Saw Palmetto May Be of No Benefit in the Treatment of Benign Prostatic Hyperplasia.:N Engl J Med. 2006;354:557-566, 632-634.News Author: Laurie Barclay, MD.CME Author: D谷sir谷e Lie, MD, MSEd.Release Date: February 8, 2006; Valid for credit through February 8, 2007
Feb. 8, 2006 〞 Saw palmetto is of no benefit in the treatment of benign prostatic hyperplasia (BPH), according to the results of a randomized, double-blind study published in the February 9 issue of The New England Journal of Medicine. The editorialist reminds us that it is the responsibility of clinicians to inform and protect their patients from unproven therapies.
"Saw palmetto is used by over 2 million men in the United States for the treatment of BPH and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration [FDA]," write Stephen Bent, MD, from the University of California, San Francisco, and colleagues. "Although most prior randomized trials of saw palmetto have reported small improvements in the symptoms of benign prostatic hyperplasia or in urinary flow rates, these studies are limited by the small numbers of subjects enrolled, their short duration, their failure to use standard outcome measures, and the lack of information from participants concerning how effectively the placebo was blinded."
The investigators randomized 225 men older than 49 years who had moderate-to-severe symptoms of BPH to 1 year of treatment with saw palmetto extract (160 mg twice a day) or with a matched placebo capsule. Primary endpoints were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate, and secondary endpoints included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects.
During the 1-year study, the change in AUASI scores was not significantly different between the saw palmetto and placebo groups (mean difference, 0.04 point; 95% confidence interval [CI], -0.93 to 1.01). Also, there were not any significant differences in maximal urinary flow rate (mean difference, 0.43 mL/minute; 95% CI, -0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen (PSA) levels. Both groups had a similar incidence of adverse effects.
"In this study, saw palmetto did not improve symptoms or objective measures of BPH," the authors write.
The authors note several factors that could explain the discrepancy between this negative study and prior evidence: effective blinding; the possibility that the participants in this study had attributes that made them less likely to have a response to saw palmetto; and the level of active ingredient in the extract possibly insufficient to produce a measurable effect.
The National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Complementary and Alternative Medicine supported this study. Three authors have disclosed various relevant financial relationships with American Medical Systems, Intuitive Surgical, Merck, TAP, GlaxoSmithKline, Pfizer, and/or Merck.
In an accompanying editorial, Robert S. DiPaola, MD, and Ronald A. Morton, MD, from the University of Medicine and Dentistry of New Jersey in New Brunswick, note that this study tested a specific preparation of saw palmetto, leaving open the possibility that a different preparation or dose of saw palmetto might have been effective.
"Even with the best regulatory provisions for herbal products, reasonable assurance of their long-term efficacy and safety will require clinical trials of the same quality required for the approval of standard drugs and, possibly, the development of pure compounds, Drs. DiPaola and Morton write. "Until there is adequate research on an herbal or other botanical product, it is the responsibility of physicians to inform their patients and protect them from the inherent risks of unproven therapies."
Drs. DiPaola and Morton have disclosed no relevant financial relationships.
Clinical Context
According to the authors, saw palmetto is used by more than 2 million men in the United States for the treatment of BPH and is commonly recommended as an alternative to FDA-approved drugs. In 2002, 1.1% of the adult US population (about 2.2 million adults) reported using saw palmetto. While randomized trials have reported some benefit to symptoms of BPH with saw palmetto, according to the authors, such studies enrolled small numbers of patients, may not have adequately blinded patients and were of short duration, and only 1 systematic review used the validated AUASI as a measure of symptom improvement.
The current study is a randomized, double-blind placebo-controlled trial comparing 160 mg twice daily of saw palmetto with identical placebo for 1 year to examine symptom improvement, prostate size and function, and quality of life in men with moderate to severe BPH.
Study Highlights
Inclusion criteria were men older than 49 years from 2 hospitals and the surrounding community, with moderate to severe BPH symptoms, AUASI score of at least 8, and peak urinary flow of less than 15 mL/second.
Exclusion criteria were high risk for urinary retention, a history of prostate cancer, surgery for BPH, urethral stricture or neurogenic bladder, creatinine level of more than 2.0 mg/dL, and PSA level of more than 4.0 ng/dL.
All participants were assigned to a 1-month, single-blind, placebo run-in period and excluded if their rate of adherence was less than 75% as determined by a capsule count.
The saw palmetto extract in the form of a soft gelatin gel capsule contained 90.7% of total fatty acids and 0.33% of total sterols. Placebo gels contained polyethylene glycol-400, a bitter tasting liquid with oily appearance and no free fatty acids.
Patients were advised to take the medication twice daily with meals.
Primary outcomes were change in AUASI score from baseline and peak urinary flow rate.
The AUASI is a 7-item, self-administered questionnaire with scores from 0 to 35 (0 - 7 indicates mild symptoms, 8 - 19 indicates moderate symptoms, and 20 - 35 indicates severe symptoms).
Secondary outcomes were changes in quality of life using the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) and BPH Impact Index, prostate size measured by transrectal ultrasound, residual volume after voiding measured by BladderScan, self-reported adverse effects and changes in levels of PSA, creatinine, testosterone, and other laboratory values.
Analyses of the subgroups were conducted for moderate vs severe symptoms, high vs low prostate volume, and high vs low PSA levels.
Patients made a total of 8 clinic visits for 14 months.
112 men were assigned to saw palmetto and 113 to placebo.
Completion rate was 96%, and adherence rate was 92% for both groups.
Mean age was 63 years, 82% were white, mean years of education was 16, baseline mean AUASI score was 15.5, residual volume after voiding was 81 mL, and mean prostate volume was 34.5 mL.
Both groups had a small decrease in AUASI scores during the 1 year: 0.68 for the saw palmetto and 0.72 for the placebo group, with no significant difference between them for change in score over time.
A clinically meaningful change in AUASI score for BPH was defined by the authors to be at least 3.0 points.
There was no significant difference in change in peak urinary flow rate, prostate size, residual volume after voiding, the BPH Impact Index, SF-36 score, serum creatinine, PSA, and testosterone levels between the groups.
The analyses of the subgroups revealed no evidence of an effect among men with more or less severe symptoms or smaller or larger prostate size.
The adequacy of blinding was assessed by asking participants to guess whether they received saw palmetto or placebo. At 12 months, 40% of men in the saw palmetto group believed they were taking the extract vs 46% in the placebo group.
The number of serious adverse events was not significantly different between the 2 groups (8 in the saw palmetto and 18 in the placebo group).
There were no significant differences in nonserious adverse events.
Pearls for Practice
Saw palmetto at 160 mg twice daily for 1 year compared with placebo does not significantly improve BPH symptoms or peak urinary flow rate in men with moderate or severe BPH.
Saw palmetto at 160 mg twice daily for 1 year compared with placebo is not associated with excess adverse events and does not improve quality of life, residual volume after voiding, or laboratory parameters in men with BPH.
Saw Palmetto Extract Effective in Treating Chronic Prostatitis.:Emma Hitt, PhD.AUA 98th Annual Meeting: Abstract 103937. Presented April 26, 2003.
April 28, 2003 (Chicago) 〞 Permixon, a compound extracted from the fruit of the American dwarf palm tree Serona repens, also known as saw palmetto, appears to improve symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
Mesut Remzi, MD, from the Department of Urology at the University of Vienna in Austria, and colleagues presented their findings here at the annual meeting of the American Urological Association.
"Although antimicrobial treatment is usually successful in men with bacterial prostatitis, currently no standardized treatment is available for Category III CP/CPPS," Dr. Remzi and colleagues point out.
The researchers evaluated the efficacy and safety of Permixon in 61 patients with Category IIIB CP/CPPS.
Men were enrolled in two institutions and randomized to six weeks of active treatment with 160 mg Permixon twice daily (n = 32) or a control group, which did not receive a placebo (n = 24). Age, prostate volume, and prostate-specific antigen (PSA) levels were comparable between groups.
The researchers evaluated the response to therapy at six and 12 weeks after treatment based on several efficacy parameters. These included Patients Subjective Global Assessment (SGA); the total NIH Chronic Prostatitis Symptom Index (CPSI); the pain, voiding, and quality of life/impact domains of the CPSI; safety data; PSA level; and prostate volume.
Seventy-five percent of the patients who received Permixon had at least mild improvement in symptoms compared with 20% of the control group. Similarly, 55% of patients who received Permixon reported moderate or marked improvement compared with 16% of the control group. After six weeks, 38% of patients treated with Permixon showed a 30% reduction in total NIH-CPSI compared with 12.5% of the control group, although no difference in this score was observed after 12 weeks.
Despite the improvement in symptoms, prostate volume did not change significantly in either group. In the control group, PSA did not differ from baseline. However, the group taking Permixon experienced median decreases from baseline PSA of 22% after 6 weeks.
According to Dr. Remzi, previous studies have indicated that Permixon has an effect on benign prostatic hyperplasia (BPH) and that it might have an impact on prostatitis.
"Currently, it is the number one treatment for BPH in France and it is also very popular in Germany and Austria for BPH," he told Medscape.
Dr. Remzi suggested that Permixon might treat CP/CPPS by exerting an influence on levels of dihydrotestosterone, or it might exert an anti-inflammatory effect or act as an alpha-blocker.
"Because of these findings, we are now going to do a placebo-controlled trial," he added.
"This study is provocative and interesting," said J. Curtis Nickel, MD, from the Department of Urology at Queen's University in Kingston, Ontario, Canada. "This type of study is what has to be done 〞 we have to look at everything and compare it to placebo, since herbal therapies may have a role to play in many of these patients." Dr. Nickel estimated that 20% to 30% of his prostatitis patients have tried saw palmetto.
"This is the first study that I know of that has showed a benefit in CP/CPPS for saw palmetto. The study should be repeated with larger numbers and we may be able to show that this type of phytotherapeutic agent may be of benefit," he told Medscape.
Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia.:Claus G. Roehrborn, MD.
Introduction
Basic research and translational and clinical investigations into lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) have been an important part of the American Urological Association (AUA) national meetings during the last 10-15 years. In 2005, 116 presentations were given as discussed or moderated posters, as well as podium presentations, representing 6.7% of the total number of 1722 presentations. This number, which has varied slightly over the years, reflects the importance of this topic to both researchers and the practicing urologist attending the AUA meetings. The 116 presentations were divided in 40 discussed posters in the basic research session, 20 moderated posters in the session of epidemiology and natural history/evaluation of LUTS and BPH, 12 podium presentations, and 20 moderated posters on surgical therapy and new technologies, and 24 podium presentations divided into 2 sessions on the popular topic of medical and hormonal therapy.
Epidemiology, Natural History, and Evaluation of BPH
It has long been known that men with BPH harbor chronic inflammatory infiltrates in 30% to 60% of cases as evidenced by specimens obtained by transurethral resection of the prostate (TURP). However, the importance of these chronic inflammatory infiltrates has never been fully elucidated. Roehrborn and colleagues[1] examined baseline biopsy specimens from participants in the Medical Therapy of Prostatic Symptoms (MTOPS) study and showed that approximately 40% had chronic inflammatory infiltrates. Men with chronic inflammatory infiltrates in general were slightly older, had larger glands (41 vs 37 mL), and had higher serum prostate-specific antigen (PSA) levels (3.3 vs 2.5 ng/mL), whereas all other baseline parameters were identical. An interesting observation was made regarding the fate of these patients in the placebo or nontreated group in the MTOPS study. During an average follow-up of 4.5 years, overall progression was noted in 13.2% of patients without inflammatory infiltrates but in 21% of patients with inflammatory infiltrates (P = .08). Similar increases in the rate of progression were noted for symptom progression and invasive therapy. Most notably, however, no patient without inflammation in a baseline biopsy specimen experienced acute urinary retention (AUR), whereas in the patients with inflammatory infiltrates, the AUR rate was 5.6%. These data suggest that the presence or absence of chronic inflammatory infiltrates in baseline biopsy specimens has a profound impact on the natural history and progression of BPH and LUTS.
A strong relationship between severity of LUTS and sexual dysfunction has been demonstrated in a multitude of studies during the past years. In this session, 2 groups presented additional corroborative data. Crawford and coworkers[2] examined the Sexual Health Inventory for Men (SHIM) questionnaire and correlated it with LUTS severity based on the categorization of mild, moderate, and severe symptoms in 6078 men who participated in Prostate Cancer Awareness Week. After controlling for age and other factors, the mean SHIM score was 17 for patients with mild LUTS, 14 for patients with moderate LUTS, and 11 for patients with severe LUTS, with a lower SHIM score suggesting greater sexual dysfunction. Van Dijk and associates[3] looked at a similar question by means of a meta-analysis of 10 large-scale surveys that involved more than 30,000 men. By multivariate analyses, they showed LUTS to be a risk factor for erectile dysfunction, ejaculatory dysfunction, and, in some trials, decreased libido. However, due to the observational and mostly cross-sectional nature of these studies, causality cannot be implied.
Several authors were interested in longitudinal changes in prostate volume, PSA, and symptom severity, as well as the association among these changes. Bosch and Bohnen[4] analyzed changes in prostate volume and their ability to predict changes in symptom score throughout 4 years in the population-based Krimpen study. Of 864 men followed up for 2 years, 8.6% and 12% had true prostate volume increases defined as an increase of 10 mL or 26%, respectively, from baseline. They observed that the chances of having a greater than 4-point increase in the International Prostate Symptom Score (IPSS) was significantly greater in the subsets of men who experienced greater volume increases, and the chances of having an improvement of greater than 3 points was lower. This study suggests that longitudinal changes in prostate volume go hand in hand with longitudinal changes in symptom severity. A similar effort was presented on behalf of the Olmsted County Study of Urinary Symptoms in Men by St Sauver and coworkers.[5] The Olmsted County study is now in its 10th year, and approximately 500 men underwent regular assessment by IPSS, PSA, flow rate, and transrectal ultrasonography volume measurement. For this particular analysis, the patients were divided by decade of life and then categorized as being either above or below the 80th percentile of PSA increase, above or below the 80th percentile of volume increase, and above the 80th percentile on the slope of the IPSS increases. When analyzing the data by either univariate or multivariate analyses, it was shown that, for a patient above the 80th percentile of the PSA increase slope or the 80th percentile of the prostate volume increase slope, the odds ratios for being above the 80th percentile of the symptom score increase slope were 2.34 and 2.32 (univariate) and 1.84 and 1.91 (multivariate).
The predictive ability of PSA and prostate volume changes over time to predict symptom worsening over time was similar to the baseline age of the patient, which again suggests that dynamic changes of volume and PSA are associated with dynamic changes of symptom severity. Lastly, de la Rosette and coworkers[6] examined the PSA velocity of 594 patients treated with watchful waiting or an alpha-blocker and followed up longitudinally in their center. Although the overall PSA velocity was 0.01 ng/mL per year, they found that a velocity of 0.5 ng/mL per year indicated increased risk of future invasive surgical therapy for BPH in these patients, again adding a dynamic component to the known predictive value of PSA regarding the natural history of BPH.
Medical and Hormonal Therapy
One of the most important trials reported at AUA 2005 was the study by Bent and coworkers[7] in which 225 men older than 40 years with a symptom score between 8 and 35 points were randomized to receive either 160 mg of saw palmetto extract twice a day or placebo for 1 year. Patients in both treatment groups experienced improvement over time; however, there were no differences in the magnitude of improvement between the 2 groups. The IPSS improvement was 2.3 vs 2.1 points in the saw palmetto vs placebo group, and the mean difference between the 2 groups in terms of maximum urinary flow rate (Qmax) was 0.23 mL/s and in terms of prostate volume was 1.2 mL, none of which were significant. This is one more trial that casts doubt on the clinical efficacy of the currently used dosage of saw palmetto berry extract (160 mg twice daily) in men with LUTS and BPH. A consortium charged by the National Center for Complementary and Alternative Medicine (NCCAM) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to study phytotherapeutic agents in LUTS and BPH is currently preparing for a trial that involves Pygeum africanum and saw palmetto compared with placebo later this summer.
Several investigators studied the relationship between LUTS and sexual dysfunction and the impact that certain alpha-blockers may have on sexual function or dysfunction. It has been stipulated that tamsulosin is unique among the alpha-blockers inasmuch as it induces ejaculatory dysfunction in a higher proportion of men compared with alfuzosin, doxazosin, or terazosin. In contrast, Barqawi and associates[8] examined data from 8076 men who participated in the Prostate Cancer Awareness Week trial and who filled in both the IPSS and the SHIM questionnaires. The mean IPSS and SHIM score were 13 and 11.7 for men taking tamsulosin, 12 and 12.7 for those taking other BPH medication, and 6.9 and 15.6 for men taking no BPH medication, respectively. After adjusting for age and IPSS, men taking tamsulosin had increases (ie, improvements) in the SHIM score, with increasing IPSS suggesting for the first time a beneficial effect of tamsulosin. Other investigators examined the role of alfuzosin and its impact on sexual function in open-label studies. Van Moorselaar and colleagues[9] examined the changes in sexual function in the main score using the Danish Prostate Symptom Score sexual-function questionnaire (DAN-PSSsex) in 3076 men taking part in a 12-month, open-label study. They showed that sexual dysfunction was more severe in patients with more severe IPSS at baseline but that improvement from baseline was also greater. Similarly, Elhilali and coworkers[10] showed significant improvements in the 5 domains of the Brief Sexual Function Inventory in men treated with a real-life practice study during 2 years with alfuzosin, 10 mg.
In an extension of the ALFAUR study published in 2005,[11] Roehrborn and colleagues[12] presented a report on men who succeeded in a trial without catheter after having been given 2-3 days of alfuzosin, 10 mg/d. Patients who continued after a successful trial without catheter following an episode of retention fare better if maintained with alfuzosin than they do with placebo, with significant reduction in the risk of secondary interventions or surgical procedures. Outcomes were predictable based on the amount of postvoid residual (PVR) and the serum PSA level with those men with higher PVRs and higher serum PSA levels being less successful in terms of avoiding surgery. This study suggests that a patient encountered in urinary retention and passing a successful trial without catheter after being given an alpha-blocker may benefit in the long term from continuation of the alpha-blocker.
Two studies that compared different alpha-blockers with no placebo control were presented. Koff and associates[13] reported on a trial that involved 165 patients with BPH who were randomized to either doxazosin gastrointestinal therapeutic system, 4 mg, vs tamsulosin, 0.4 mg/d for 12 weeks. These authors found nearly identical improvements in terms of symptom score, flow rate, and other parameters between the 2 groups but earlier onset of improvement in the doxazosin compared with the tamsulosin groups and, at 12 weeks, an increased proportion of patients reporting ejaculatory difficulties in the tamsulosin group compared with the doxazosin group. This is not a surprising finding given the higher probability of ejaculatory disturbances reported with tamsulosin compared with other alpha-blockers. In a related study, Wyllie and colleagues[14] asked why all alpha-blockers are not equal with respect to sexual function and examined the pharmacological and binding activities of quinazoline derivatives vs tamsulosin. They showed that all displayed a high affinity for the alpha-1A, alpha-1B, and alpha-1D subtypes. However, although the quinazolines have more or less equal affinity for all 3 subtypes, tamsulosin has selectivity for alpha-1A and alpha-1D. An important finding is that tamsulosin at concentrations in the lower urinary tract tissues that are achieved at either 0.4- or 0.8-mg/d dosing demonstrated considerable interaction at serotonin (5-HT1A) and dopamine (D3) receptors. Taking these data together with other findings reported by Hellstrom and coworkers[15] during this year's AUA meeting, it is reasonable to assume that the selectivity for the serotonin and dopamine receptors exhibited by tamsulosin might be responsible for the increased incidence of ejaculatory disturbances. Matsukawa and colleagues[16] randomized 144 patients to an alpha-1D selective alpha-blocker (naftopidil) or tamsulosin. The interest in this trial stems from the observation and suggestion that the alpha-1D receptor is overexpressed in the obstructed detrusor muscle and, thus, that blocking the alpha-1D receptor might be important in treating irritative symptoms, such as urgency, frequency, and nocturia. However, in contrast to the theoretical consideration, patients in both groups experienced similar improvements in the IPSS, quality-of-life score, urinary flow rate, and residual urine but also in the irritative and obstructive subscores of the IPSS. It is suggested, therefore, that the selective inhibition of the alpha-1D receptor does not yield superior results in terms of irritative symptoms.
Although an equal number of abstracts concentrated on 5alpha-reductase inhibitors, most data were presented regarding the dual inhibitor dutasteride. Marks and coworkers[17,18] presented 2 abstracts on the transition zone hypothesis. It has been suggested that 5alpha-reductase inhibitors have a stronger effect on the transition zone of BPH glands compared with the peripheral zone, because the transition zone is the source and origin of BPH. By analyzing the data from the phase 3 dutasteride program, the study authors demonstrated, however, that the volume shrinkage is identical in the transition and peripheral zones and that the transition zone index calculated as the transition zone over the total prostate volume remains at 0.5 from baseline to 24 months of follow-up and is the same for placebo and dutasteride. Thus, there is no differential effect noted of 5alpha-reductase inhibitors on the different zones in the prostate. In the second part of this analysis, it was shown that the efficacy compared with placebo increases with dutasteride in men with larger prostates and with higher transition zone index tertiles. Both larger prostate volumes and higher transition zone indices are associated with larger net improvement in terms of IPSS and a greater odds ratio for placebo vs dutasteride-treated patients who experience either AUR or surgery.
The question has been raised whether the improvements obtained with 5alpha-reductase inhibitors are clinically significant, since the actual numerical improvements in symptom score appear to be less with 5alpha-reductase inhibitors compared with alpha-blockers. Roehrborn and colleagues[19] addressed this issue by analyzing data from the dutasteride phase 3 trial program. By stratifying the patients according to symptom severity at baseline into those with moderate vs severe symptoms, they showed an improvement in symptom score of 4.9 points in the group that was moderately symptomatic at baseline and 10.1 points in the group that was severely symptomatic at baseline, both differences being highly significant statistically and clinically. This is based on an observation by Barry and colleagues[20] published in The Journal of Urology in 1995 that an improvement of more than 2 points was needed in patients with baseline scores less than 20 points and of more that 6 points in patients with baseline scores above 20 points (ie, in the severely symptomatic range) to achieve a clinically meaningful improvement. According to this classification, patients treated for 48 months with dutasteride had a 74% probability of achieving a clinically significant improvement regardless of baseline severity.
Several abstracts focused on further analyses of the MTOPS trial. The role of PVR was examined in detail by Roehrborn and coworkers.[21] PVR has been shown to correlate poorly with other baseline parameters, such as symptom severity, Qmax, and prostate volume, and has been found to be predictive of outcomes or symptom improvement. In the MTOPS study, baseline PVR was stratified into 4 quartiles, and overall progressions were calculated for the 4 treatment groups. The highest PVR quartile in the placebo group had the highest rate and relative risk of clinical progression overall, and when analyzing the placebo group for overall progression, symptom progression, and AUR, it appears that both symptomatic progression and overall progression are significantly more likely in patients with higher baseline PVR values. In all 4 treatment groups, there was a trend for the patients who experienced AUR to start out with higher baseline AUR values and to experience an ever-increasing amount of PVR until finally culminating in the AUR event. This suggests that AUR episodes in patients with LUTS and BPH are often preceded by an ever-increasing amount of PVR, ultimately leading to a decompensation of the bladder and the AUR event. Another approach to analyzing predictors of outcomes such as AUR or surgery in the MTOPS study was undertaken by Slawin and colleagues.[22,23] They used a nomogram approach to predict symptomatic progression, AUR, and surgery. Such nomograms allow one to take baseline characteristics, assign point values to these baseline characteristics, and calculate with reasonable clinical certainty whether symptom progression, AUR, or surgery events will occur in the subsequent 2-4 years. The study authors made a somewhat surprising finding regarding the nomogram to predict AUR or surgery. Significant predictors of AUR or surgery were age, total PSA, randomization to finasteride, and, surprisingly, the BPH Impact Index, a comparatively underused parameter. In contrast, peak urinary flow rate or the IPSS were not predictive of episodes of AUR or surgery. In models that included prostate volume measurements, PSA did not prove to be predictive presumably because of the high correlation between PSA and prostate volume parameters. Nomograms of this nature are popular and often used in prostate cancer clinical prediction models. They might very well find a niche in predicting the progression and natural history of LUTS and BPH.
Minimally Invasive Therapies and Surgical Interventions
Two studies were presented regarding the controversial treatment of injecting botulinum toxin (BTX) intraprostatically, and their results could not be more conflicting. The first, by Larson and coworkers,[24] presented initial data on a pilot group of 10 patients treated in a noncontrolled manner with 150 U of BTX on either side of the prostate. The results showed significant improvement in patients' symptoms. Larson and coworkers also reported on a randomized trial that involved 30 patients with LUTS and BPH. These patients were randomized 2:1 to receive either 100 U of BTX on each side vs a similar volume injection of normal saline solution. Over time, both groups experienced identical improvements in symptoms, flow rate, and other parameters, suggesting no real benefit above and beyond a sham effect. In contrast, an Italian group studied 16 patients treated with a total of 300 U of BTX intraprostatically.[25] These patients were followed up for 6 months but without a control group. The findings showed a significant improvement in symptom score from 24 to 9 points, flow rate improvements from 8.2 to 18 mL/s, and, most remarkably, a decrease in the prostate size from 106 to 53 mL. Based on these conflicting data, it is fair to say that at this time BTX injection in the prostate as a treatment for LUTS and BPH cannot be endorsed as a validated and accepted treatment.
Several abstracts were presented on microwave thermotherapy. Albala and colleagues[26] updated the data on the TherMatrx TMX-2000 device. Of the original 200 patients treated with this device, 33 have now been followed up for up to 60 months, and the results in those who have been followed up were durable, with a symptom score improvement of 21.4 to 12.4 and a flow rate improvement of 8.6 to 13.6 mL/s. However, because of the nature of the follow-up (mail-in questionnaires), re-treatment rates in those patients who had not been followed up are not known.
Data on a study in 120 patients in urinary retention randomized to either TURP or Prostalund feedback thermotherapy were presented by Schelin and associates.[27] Ninety percent of patients treated with TURP became catheter free vs 80% in the thermotherapy group. Improvement in symptoms and flow rate were similar between the 2 groups. Thus, the Prostalund feedback thermometry unit might be suitable for patients who present with AUR and not only for those with symptomatic BPH. Roehrborn and colleagues[28] updated the Urologix Cooled ThermoCath (CTC) multicenter trial. At 24 months, the symptom improvement with the CTC treatment catheter resulted in an improvement in symptom score from 20.8 to 9.9 points and an improvement in urinary flow rate from 8.3 to 11.8 points. Both absolute and percentage improvements with this 28.5-minute treatment are comparable to the older style Targis system treatment that had a 60-minute treatment time.
Two abstracts presented findings concerning treatment outcomes with the interstitial laser coagulation (ILC) Indigo Optima Laser. The first[29] featured an innovative design, namely, a randomization between ILC Indigo Optima Laser and tamsulosin, 0.4 mg/d. This initial report on those patients who have finished 6 months of follow-up demonstrated an improvement from 23.2 to 11.4 points in the IPSS for the ILC group vs an improvement from 24.4 to 19.2 in the tamsulosin group.
Clearly, the data are not mature enough and the number of patients followed up not large enough to draw firm conclusions, but since this is only the second trial to randomize patients to either medical therapy or minimally invasive therapy, the data should be watched with great interest. Mitsumori and associates[29] identified factors associated with failure of ILC using the Indigo Optima Laser device. They reported that patients with Schafer grade obstruction of greater than 3 had a significantly higher rate of failure as did those with total prostate volumes of less than 41 mL. This finding suggests that the Indigo Optima Laser technology is most suited for patients with moderate obstruction and true hyperplasia of the prostate (ie, enlarged prostate glands).
A number of abstracts focused on the potassium titanyl phosphate (KTP) or GreenLight laser, a process known as photoselective vaporization of the prostate (PVP). This technology is produced by LaserScope Corporation. PVP with this device has found widespread acceptance both in the United States and abroad, since the procedure is similar to the ablation of prostate tissue with the old-style right-angle laser fibers and since the learning curve is not as steep as it is for procedures such as the Holmium resection or enucleation of the prostate. Te and colleagues[30] reported on the initial 200 patients treated at New York Presbyterian Hospital. These patients had a mean prostate volume of 89 mL and were treated in an average of 96 minutes with intravenous sedation or spinal or general anesthesia. All except 5 patients were discharged within 23 hours. The symptom score at the point of latest follow-up had improved from 18.4 to 7.9 and the flow rate from 8.5 to 16.6 mL/s. Re-treatments were comparatively rare; only 3 patients required re-treatment at 12 months of follow-up. Peterson and coworkers[31] reported on 42 patients in urinary retention compared with 56 patients who were not in retention and found similar postoperative catheterization times and similar outcomes in terms of symptom score and urinary flow rate. Postoperative retention that required recatheterization occurred in 19% vs 11% in both groups, respectively. Equally good results with the PVP procedure were reported from Europe by Bachmann and colleagues,[32] Reich and colleagues,[33] Sulser and colleagues,[34] and Bouchier-Hayes and colleagues.[35] Sulser and coworkers compared PVP and TURP in a nonrandomized prospective study, while Bouchier-Hayes and colleagues presented data from a randomized trial comparing these 2 modalities.
Matlaga and coworkers[36] reported on their experience with Holmium laser enucleation of the prostate (HOLEP) and specifically addressed the issue of the decrease in serum PSA level. In 116 patients, the PSA level decreased from a preoperative mean of 7.32 ng/mL to a postoperative mean of 1.04 ng/mL or 88.8%. This finding suggests a near total removal of all transition zone tissue similar to that achieved by a well-performed TURP or an open enucleation of the prostate. Peterson and colleagues[37] reported on 164 patients treated in urinary retention with a mean prostate weight of 107 g who underwent the HOLEP procedure. An average of 82 g was removed in an average of 98 minutes, with a mean catheterization time of 22 hours and a length of stay of 35 hours. The symptom score fell at 6 months to 4.0 points, with a mean peak flow rate of 24 mL/s.
Summary:
The AUA 2005 again provided a great depth of presentations regarding LUTS and BPH. Although we still do not understand the ultimate cause of BPH, basic research findings advance our understanding of its etiology and perhaps point to new areas of therapeutic targeting. Natural history studies demonstrate that the interrelationship among prostate volume, PSA, and symptom severity is a dynamic one inasmuch as changes in one parameter seem to be predictive of changes in another parameter. Insights from medical therapy studies with alpha-blockers, 5alpha-reductase inhibitors, and combination therapy allow us to use different medications either alone or in combination in a more differentiated way, thus improving the efficacy of the treatment and ultimately the cost-effectiveness. In the area of minimally invasive treatments and surgical technologies, it appears that the KTP or GreenLight laser has gained considerable popularity due to the ease of its use and the rapid learning curve. The results are still considered to be short to intermediate term and therefore not mature. Concern has been raised regarding the completeness of the ablation of the tissue in large glands and the potential of re-treatment rates being higher than after a standard TURP. The answer to this question will come from appropriate long-term outcome studies. Regarding HOLEP, it appears that the long-term outcomes are indeed excellent, and the significant decrease in PSA level observed suggests that all available tissue from the transition zone is effectively removed, thus, in all likelihood predicting a very low rate of re-treatment.
References:
1.Roehrborn C, Kaplan S, Noble W, et al. The impact of acute or chronic inflammation in baseline biopsy on the risk of clinical progression of BPH: results from the MTOPS study. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1277.
2.Crawford E, Barqawi A, O'Donnell C, Mills J, Roehrborn C. The correlation between LUTS (AUA-SS) and erectile dysfunction (SHIM) in an age matched racially diverse male population: data from the prostate cancer awareness week (PCAW). Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1285.
3.van Dijk M, Skrekas T, Wijkstra H, de la Rosette J. Lower urinary tract symptoms and sexual dysfunction: a confirmed association. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1292.
4.Bosch J, Bohnen A. The relationship between true change in prostate volume and significant change in AUA symptom index (>/=4 points) in a population-based study of men aged 50-78 years after 4.2 years of follow-up: the Krimpen study. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1280.
5.St Sauver J, Jacobson D, McGree M, Girman C, Lieber M, Jacobsen S. Associations between longitudinal changes in prostate volume, prostate specific antigen, and peak urinary flow rates and changes in urinary symptoms. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1283.
6.de la Rosette J, Mochtar C, Kiemeney L, van Riemsdij M, Debruyne F, Laguna M. PSAS velocity in BPH: characteristics and its value to predict BPH-related invasive therapy. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1290.
7.Bent S, Kane C, Shinohara K, Goldberg H, Neuhaus J, Avins A. A randomized controlled trial of saw palmetto for the treatment of benign prostatic hyperplasia. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1637.
8.Barqawi A, O'Donnell C, Roehrborn C, Crawford E. The observed effect of Flomax intake on sexual health in men with lower urinary tract symptoms: analysis from the prostate cancer awareness week (PCAW). Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1699.
9.Van Moorselaar J, Harving N, Matzkin H, et al. Improvement of sexual function with alfuzosin 10 mg once daily is related to baseline LUTS and bother severity. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1701.
10.Elhilali M, Vallancien G, Van Moorselaar J, et al. Beneficial effects of alfuzosin 10 mg OD on LUTS, quality of life and sexual function: a 2-year experience in BPH patients in real life practice. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1707.
11.McNeill SA, Hargreave TB, Roehrborn CG, Alfaur study group. Alfuzosin 10 mg once daily in the management of acute urinary retention: results of a double-blind placebo-controlled study. Urology. 2005;65:83-90.
12.Roehrborn C, Hargreave T, McNeill S, Naadimuthu A, Beffy J. Prostate specific antigen (PSA) and post void residual (PVR) urine volume predict relapse of urinary retention and need for surgery in patients with benign prostatic hyperplasia (BPH) after a first episode of acute urinary retention (AUR). Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1635.
13.Koff W, Bertero E, Pinheiro G, et al. A randomized, double-blind study comparing the efficacy and tolerability of controlled-release doxazosin and tamsulosin in the treatment of benign prostatic hyperplasia. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1643.
14.Wyllie M, Bay H, Andersson K. Why all alpha-blockers are not equal with respect to sexual function. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1641.
15.Hellstrom W, Smith W, Sikka C. Effects of alpha-blockers on ejaculatory function in normal subjects. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 874.
16.Matsukawa Y, Gotoh M, Kamihira O, Ono Y, Ohshima S. Do two alpha1 adrenergic receptor antagonists with different affinity to alpha1 subtypes of alpha1A and alpha1D make any difference in clinical efficacy in patients with benign prostatic hyperplasia? randomized controlled trials of naftopidil and tamsulosin. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1702.
17.Marks L, Wolford E, Wilson T, Roehrborn C. Transition zone hypothesis in benign prostatic hyperplasia. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1703.
18.Marks L, Wolford E, Wilson T, Roehrborn C. Ability of the transition zone index to predict changes in symptoms and maximum flow rate in men with BPH treated with placebo versus dutasteride. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1704.
19.Roehrborn C, Siami P. Clinically meaningful (perceptible) changes in symptom scores during long-term dutasteride therapy in men with benign prostatic hyperplasia. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1646.
20.Barry M, Williford W, Chang Y, et al. Benign prostatic hyperplasia specific health status measures in clinical research: how much change in the American Urological Association Symptom Index and the Benign Prostatic Hyperplasia Impact Index is perceptible to patients? J Urol. 1995;154:1770-1774.
21.Roehrborn C, Kaplan S, Lee M, et al. Baseline post void residual urine volume as a predictor of urinary outcomes in men with BPH in the MTOPS study. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1638.
22.Slawin K, Roehrborn C, McConnell J, et al. Development of a nomogram to predict symptom progression with or without medical therapy in men with BPH based on data from the MTOPS trial. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1639.
23.Slawin K, McConnell J, Roehrborn C, et al. Development of a nomogram to predict acute urinary retention or BPH-related surgery with or without medical therapy in men with BPH based on data from the MTOPS trial. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1640.
24.Larson T, Huidobro C, Acevedo C, Mynderse L, Larson B. Intraprostatic injection of botulinum toxin in the treatment of symptomatic LUTS, including sequential MRIs for accurate changes in size of the prostate. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1386.
25.Guercini F, Giannantoni A, Bard R, et al. Intraprostatic botulin toxin injection in patients with severe benign prostatic hyperplasia: a multicenter feasibility study. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1387.
26.Albala D, Andriole G, Davis B, et al. Transurethral microwave thermotherapy (TUMT) using the thermatrx TMX-2000TM: long-term results in a study comparing TUMT with a sham procedure in patients with benign prostatic hyperplasia (BPH). Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1551.
27.Schelin S, Walter S, Geertsen U, et al. Benign prostatic hyperplasia in chronic urinary retention 每 a prospective randomized multicenter study 每 Prostalund feedback treatment vs surgical treatment. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1552.
28.Roehrborn C, Mynderse L, Partin A, Preminger G, Cote E, Larson T. Intermediate results of a multi-center trial of a new generation cooled TUMT for BPH. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1553.
29.Mitsumori K, Nishizawa K, Kawahara T, Watanabe J, Kobayashi T, Ogura K. Factors associated with failure of interstitial laser coagulation in the treatment of benign prostatic hyperplasia. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1567.
30.Te AE, Jaspreet S. Sandhu, Balaji Reddy, et al. The first 200 patients treated with high-power KTP photoselective laser vaporization prostatectomy: the New York Presbyterian experience. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 823. A1561, P423, 2005.
31.Peterson M, Matlaga B, Kim S, et al. Holmium laser enucleation of the prostate (HOLEP) for men with urinary retention. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1560.
32.Bachmann A, Ruszat R, Seifert H, Casella R, Wyler S, Sulser T. Photoselective vaporization of the prostate (PVP) in men with preoperative catheterization due to chronic urinary retention. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1566.
33.Reich O, Bachmann A, Zaak D, Hofstetter A, Sulser T, Stief C. Photoselective vaporization of the prostate (PVP): Prospective evaluation in 85 high risk patients. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1557.
34.Sulser T, Schurch L, Ruszat R, Reich R, Lehmann K, Bachmann A. Prospective comparison of photoselective laser vaporization (PVP) and transurethral resection of the prostate (TURP). Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1558.
35.Bouchier-Hayes D, Anderson P, Van Appledorn S, Bugeja P, Costello A. A randomized trial comparing photo-vaporisation and trans-urethral resection of the prostate in patients. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1555.
36.Matlaga B, Kim S, Kuo R, Watkins S, Lingeman J. Holmium laser enucleation of the prostate: the effect of a minimally invasive treatment modality on serum prostate specific antigen. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1559.
37.Peterson M, Matlaga B, Kim S, et al. Holmium laser enucleation of the prostate (HOLEP) for men with urinary retention. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 1560.
Saw Palmetto for Benign Prostatic Hyperplasia.:Allan S. Brett, MD.Bent S et al. Saw palmetto for benign prostatic hyperplasia.N Engl J Med 2006 Feb 9; 354:557-66.
Summary:Extracts of the berries of saw palmetto, a small palm tree native to the southeastern U.S., are used widely to treat benign prostatic hyperplasia (BPH). In this randomized trial conducted in California, 225 men with moderate-to-severe symptoms of BPH received either saw palmetto extract (160 mg twice daily) or placebo. Patients were not permitted to use 汐-blocking drugs or 5汐-reductase inhibitors during the trial.
During 1 year of treatment, no significant differences were noted between saw palmetto recipients and placebo recipients in the two primary outcomes 〞 mean American Urologic Association symptom scores and peak urinary flow rate. In addition, no differences were seen in secondary endpoints, such as quality of life scores, sexual function scores, residual urine volume, and prostate volume.
Comment:The finding of this trial 〞 no benefit for saw palmetto 〞 should be taken seriously. The trial was conducted according to rigorous methodologic standards, and the authors discuss methodologic reasons (including the adequacy of blinding) why their results might differ from those of previously published positive trials. When results of an herbal remedy trial are negative, critics often respond that the extract used in the study might not have been representative of biologically active products. However, the chemical content of the extract used in this study met criteria proposed by alternative medicine experts.
Is Herbal Medicine Science or Pseudoscience?:Sarah T. Corley, MD, FACP
A Spotty Regulatory History:
Today's explosion in "alternative medicine" might best be seen in the context of hundreds of years of medical claims and rumors, noted Katherine Gundling, MD, FACP. Some of the earliest well-documented food adulteration and purity laws are attributed to the ancient Hebrews. Other historic efforts included the Assize of Bread, the first English food law. Announced in 1202 by King John, the proclamation prohibited adulteration of bread with ground peas or beans.
During the mid-1800s, European medications of questionable safety were widely marketed in the United States. One consequence was the Drug Importation Act of 1848, said Dr. Gundling, who is Assistant Professor and Director of Medical Education at the Department of Internal Medicine, University of California at Davis. Increasingly stringent laws were passed during the 19th and early 20th centuries in an effort to safeguard the purity and safety of serums, vaccines, and other therapeutic agents. On June 30, 1906, the original Pure Food and Drugs Act was passed, conferring misdemeanor status on the interstate commerce of adulterated and mislabeled substances. On the same day, the Meat Inspection Act was also enacted; partly in reaction to widespread outrage following publication of Upton Sinclair's The Jungle, which documented unhealthy meat handling practices.
The 19th century also saw the development of osteopathy, homeopathy, and chiropractic. After a 1907 US survey on quality of instruction in medical schools, all but 4 homeopathic schools closed. Those that remained were Hahnemann (named for the founder of homeopathy, Samuel Hahnemann), Boston University, New York Homeopathic Medical College, and the University of Michigan.
In another effort to combat abuses in the food and drug industries, the newly formed US Food and Drug Administration (FDA), in 1930, recommended a complete overhaul of the 1906 Act. Ultimately, in 1938, the Food, Drug, and Cosmetic Act was passed, in large part because of 107 deaths traced to an elixir made with a toxic solvent. The 1938 Act mandated more informative labeling, evidence of safety prior to marketing, authorization of factory inspections, increased government authority for enforcement and seizure, and requirements for new drug applications. The Durham-Humphrey Amendment of 1951 defined which substances would require a prescription and medical supervision.
The Move to Deregulate
Proposals to regulate vitamins and minerals led to the Proxmire Amendments in 1976, which restricted the FDA from setting standards limiting potency. The landmark 1990 Nutritional Labeling and Education Act permitted some health claims to be made for foods and supplements.
In 1994, the Dietary Supplement Health and Education Act (DSHEA) defined dietary supplements and excluded them from the definition of food additives. Although the safety of supplements resides with manufacturers, the determination and burden of proof lies with the FDA. Botanical labels must include, among other things, the name of the product, the plant's Latin name, amounts per dose, and the following disclaimer: "This product has not been evaluated by the FDA. This product is not intended to diagnose, mitigate, treat, or cure any disease." Manufacturers are no longer routinely required to prove that listed ingredients are present in listed amounts. The government may test supplements and pursue redress if inaccuracies are found. However, since funds and manpower are insufficient to test everything on the market, there is a potential for supplements to be sold without active ingredients, lacking standardization, and even containing contaminants. The Internet is one of the factors in the rapid transfer of information -- accurate or not -- contributing to a huge surge in the number of consumers purchasing unregulated supplements.
Do Studies Support Herbal Claims?
In the current climate of loose regulation, 7 strategies might be helpful when attempting to select a safe and effective herbal product, suggested Norman Farnsworth, PhD, of the College of Pharmacy, University of Illinois.
The manufacturer should be in business for at least 5 years.
The labels should conform to DSHEA regulations.
The labeling should include a statement of standardization.
Products claiming to be a "cure" or a "miracle" should be avoided.
Extracts should be preferred over powdered plant material.
Single plant extracts are preferable to multiple plant extracts.
Whenever possible, the same brands used in reported clinical trials should be sought.
In Women's Health:
Guidelines are soon expected from the FDA on the use of soy products to lower cholesterol; studies have shown significant drops in total cholesterol and low-density lipoprotein cholesterol and slight increases in high-density lipoprotein cholesterol with the consumption of 47 g of soy protein per day.
When it comes to soy's ability to alleviate menopausal symptoms, however, the data are not definitive, reported Fredi Kronenberg, PhD, of Columbia University School of Public Health, New York City. Although studies are numerous, meta-analysis has not been feasible since amounts and types of soy products have varied and patient populations have differed. And in most studies, no significant reduction of symptoms has been found. Complicating the picture is the strong placebo effect seen in menopausal studies, Dr. Kronenberg said. Yet soy does contain phytoestrogens, and epidemiologic studies suggest it may have a bone-conserving effect. Some researchers cite the lower incidence of osteoporosis in Asian women, but prospective studies are lacking. Ongoing studies are investigating soy as a vasodilator, anticoagulant, and antioxidant.
Although no known estrogenic substances have been isolated from black cohosh (a completely different species from blue cohosh), the preponderance of clinical evidence has shown a positive effect on menopausal symptoms when compared with placebo. Caveats include the lack of long-term studies and unknown effects on the uterus and on breast cancer. Few side effects have been reported, and this supplement may be safe and effective for short-term use.
Red clover contains 4 estrogenic isoflavones, but data on menopausal benefits are limited. One double-blind placebo-controlled study found no significant symptomatic effects, although a rise in high-density lipoprotein was noted at a 40-mg dose. (The latter finding requires further study.) Finally, a double-blind, randomized, placebo-controlled trial of dong quai found no statistically significant effect on menopausal symptoms.
Herbs for Insomnia and Anxiety?
Seven randomized controlled trials have found kava superior to placebo in reducing anxiety, reported Adriane Fugh-Berman, MD, of George Washington University School of Medicine, Washington, DC. In one study, kava reportedly matched the efficacy of oxazepam. Side effects are apparently minimal with short-term use, but an ichthyosiform dermopathy and other significant adverse effects have been reported with long-term high doses. Some concerns have been raised about kava's potential interactions with alprazolam and levodopa, although the case reports are not well documented and other drugs may have been involved. One study showed no interaction between kava and alcohol.
Valerian root extracts (both pure and mixed forms) have been found more effective than placebo for treating insomnia. Sleep latency is reportedly decreased and sleep quality is improved. An antagonistic effect on alcohol has been suggested.
Saw Palmetto, St. John's Wort, and Other Herbs in the News
Saw palmetto has been studied in 18 randomized clinical trials in men with symptomatic prostatism; 10 of the trials were placebo controlled. Significant decreases in urinary symptom scores and nocturia were reported, resembling the effects of finasteride, but with erectile dysfunction as a possible side effect. Saw palmetto inhibits 5-alpha reductase but does not affect serum prostate-specific antigen (PSA) levels.
In 23 meta-analyses of clinical trials, St. John's wort was found to be superior to placebo for the treatment of depression and comparable in efficacy to low-dose tricyclic antidepressants. No comparative trials with selective serotonin reuptake inhibitors have yet been completed. Phototoxicity is a possible side effect, and case reports of drug interactions have begun to appear, along with 7 reports of an effect on blood coagulation (5 showed a decreased international normalized ratio). Recent evidence suggests that cyclosporine levels may be lowered in patients taking St. John's wort, possibly leading to graft rejection following transplant; lower levels of indinavir -- with a potential decrease in antiretroviral effects -- have also been reported.
Studies of echinacea can be difficult to compare and interpret since the herb is available in 3 different types, said Gail Mahady, PhD, of the College of Pharmacy, University of Illinois. Some efficacy has been reported in the treatment of upper respiratory tract symptoms, but no demonstrable preventive effect has been found. Echinacea angustifolia was shown to lower viral burden in a short-term study of HIV-infected patients who received 1 g 3 times daily for 12 weeks. Further study is needed, however, as in vitro studies have shown an increase in tumor necrosis factor, which could worsen HIV infection. Echinacea should be avoided by patients with an allergy to flowers of the daisy family.
Siberian ginseng has been assessed as a "tonic and immune stimulant" in only 4 very small, randomized clinical trials, and the results were evenly split. Korean ginseng, which is distinct from Siberian ginseng, and whose active ingredients are ginsenosides, has been studied in at least 40 clinical trials. Positive effects on mood enhancement were reported in 13 of 15 controlled trials (8 double-blind); improved "physical condition" was reported in 17 trials; and "mental improvement" was reported in 11. However, the methodologies of these ginseng trials have been categorized as "relatively poor."
Although the proposed active ingredient of goldenseal -- berberine -- has antibacterial properties in vitro, no clinical trials have yet been conducted to support its use. Despite popular rumor, it apparently does not conceal illicit drug use on urine screens.
Ginkgo biloba has been studied in more than 100 clinical trials. In the 36 that have been considered well designed, standardized extracts at doses of 120 mg to 240 mg per day were used. Beneficial effects on memory were reported in all 36 trials, and studies are now under way in patients with Alzheimer's disease. Evidence suggests some benefits in patients with vertigo, but results in patients with tinnitus have been mixed, with response rates of about 50%. Drug interactions with warfarin and possibly thiazide diuretics have been reported.
Extract of horse-chestnut seed (150 mg escin per day) has been studied in 15 placebo-controlled randomized trials for the treatment of chronic venous insufficiency. Although some gastrointestinal side effects have been reported, patients also described less pain, itching, and fatigue; and lower extremity color was noted to improve -- all effects considered comparable to those of a class 2 compression stocking.
The scientific data base is growing, and researchers and clinicians are often looking at reported findings with a sharper critical eye. Simultaneously, patients often have access to more sophisticated information, but are also just as likely to come across unsubstantiated claims for "alternative" therapies. A consensus is growing that herbal remedies may have a role in the therapeutic armamentarium, but should be subject to the same rigorous tests of efficacy as more traditional approaches to treatment. More news is expected in the coming several years from better-designed clinical trials of herbal remedies.
Suggested Reading:
Blumenthal M, ed. The Complete German Commission E Monographs. Austin, Texas: The American Botanical Council;1998
Cohen M. Complementary and Alternative Medicine: Legal Boundaries and Regulatory Perspectives. Baltimore, Maryland: The Johns Hopkins University Press;1998.
Ernst E, ed. Complementary Medicine: An Objective Appraisal. Oxford, England: Butterworth-Heinemann Medical;1996.
Ernst E, Hahn EG, eds. Homeopathy: A Critical Appraisal. Oxford, England: Butterworth-Heinemann;1998.
Gevitz N, ed. Other Healers. Baltimore, Maryland: The Johns Hopkins University Press;1988.
Moore JS. Chiropractic in America: The History of a Medical Alternative. Baltimore, Maryland: The Johns Hopkins University Press;1993.
O'Connor BB. Healing Traditions: Alternative Medicine and the Health Professions (Studies in Health, Illness, and Caregiving). Philadelphia, Pennsylvania: University of Pennsylvania Press;1995.
Robbers JE, Tyler VE. Tyler's Herbs of Choice: The Therapeutic Use of Phytomedicinals. . Binghamton, New York: The Haworth Herbal Press;1998.
Sirica C. Osteopathic Medicine: Past, Present, and Future. New York: Josiah Macy, Jr, Foundation;1996.
Vincent C, Furnham A. Complementary Medicine: A Research Perspective. Chichester, United Kingdom: John Wiley and Sons, Ltd;1997.
World Health Organization. WHO Monographs on Selected Medicinal Plants, Volume 1, Geneva, Switzerland: World Health Organization;1999.
A prospective study of the efficacy of Serenoa repens, Tamsulosin, and Serenoa repens plus Tamsulosin treatment for patients with benign prostate hyperplasia.:Int Urol Nephrol. 2007 Jan 4;Hizli F, Uygur MC.Department of Urology, Oncology Education and Research Hospital, Ankara, Turkey.[PMID: 17203353]
INTRODUCTION: Increasing attention has been focused on the use of phytotherapeutic agents to alleviate the symptoms of benign prostatic hyperplasia (BPH) in recent times. The best described and studied phytotherapeutic agent is Serenoa repens (SR). MATERIALS AND METHODS: This prospective study was designed to have 3 arms including SR 320 mg per day (N = 20), Tamsulosin (TAM) 0.4 mg per day (N = 20) and SR + TAM (N = 20) to reveal the superiority or equivalence between these treatment regimens in BPH. RESULTS: The groups were not statistically different with regard to increase in maximal urinary flow rate (Q (max)) and decrease in International Prostate Symptom Score (I-PSS) (P > 0.05). No adverse effect was detected in SR therapy group. CONCLUSION: Treatment of BPH by both SR and TAM seems to be effective alone. None of them had superiority to another and additionally, combined therapy (SR + TAM) does not provide extra benefits. Furthermore SR is a well-tolerated agent that can be used alternatively in the treatment of LUTS due to BPH.
Effects of homeopathic preparations on human prostate cancer growth in cellular and animal models.:Integr Cancer Ther. 2006 Dec;5(4):362-72.MacLaughlin BW, Gutsmuths B, Pretner E, Jonas WB, Ives J, Kulawardane DV, Amri H. Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20007, USA.[PMID: 17101766]
The use of dietary supplements for various ailments enjoys unprecedented popularity. As part of this trend, Sabal serrulata (saw palmetto) constitutes the complementary treatment of choice with regard to prostate health. In homeopathy, Sabal serrulata is commonly prescribed for prostate problems ranging from benign prostatic hyperplasia to prostate cancer. The authors' work assessed the antiproliferative effects of homeopathic preparations of Sabal serrulata, Thuja occidentalis, and Conium maculatum, in vivo, on nude mouse xenografts, and in vitro, on PC-3 and DU-145 human prostate cancer as well as MDA-MB-231 human breast cancer cell lines. Treatment with Sabal serrulata in vitro resulted in a 33% decrease of PC-3 cell proliferation at 72 hours and a 23% reduction of DU-145 cell proliferation at 24 hours (P<.01). The difference in reduction is likely due to the specific doubling time of each cell line. No effect was observed on MDA-MB-231 human breast cancer cells. Thuja occidentalis and Conium maculatum did not have any effect on human prostate cancer cell proliferation. In vivo, prostate tumor xenograft size was significantly reduced in Sabal serrulata-treated mice compared to untreated controls (P=.012). No effect was observed on breast tumor growth. Our study clearly demonstrates a biologic response to homeopathic treatment as manifested by cell proliferation and tumor growth. This biologic effect was (i)significantly stronger to Sabal serrulata than to controls and (ii)specific to human prostate cancer. Sabal serrulata should thus be further investigated as a specific homeopathic remedy for prostate pathology.
Effect of biologically active substances of animal and plant origin on prooxidant-antioxidant balance in rats with experimental prostatic hyperplasia.:Eksp Klin Farmakol. 2006 Jul-Aug;69(4):66-8.Belostotskaia LI, Nikitchenko IuV, Gomon ON, Chaika LA, Bondar' VV, Dziuba VN..[PMID: 16995443]
The effect of biologically active complexes of animal (prostatilen) and plant (permixon) origin on physiological indices of prostate and prooxidant-antioxidant balance in prostate and blood was studied in rats with the hyperprolactinemia-induced prostatic hyperplasia. It was shown that both prostatilen (1 mg of the total peptides per kg) and permixon (100 mg of Serenoa repens extract per kg) prevent increase in the prostate mass and volume, in the content of lipid hydroperoxides, and in the glutathione peroxidase activity in prostate. Prostatilen, in contrast to permixon, normalized the content of lipid hydroperoxides (increased under hyperplazia conditions) and increases glutathione peroxidase activity (reduced under hyperplazia conditions).
Saw Palmetto Berry as a Treatment for BPH.:Rev Urol. 2001 Summer;3(3):134-8.Fagelman E, Lowe FC. [PMID: 16985705]
Phytotherapeutic agents are often prescribed in Europe for the treatment of benign prostatic hyperplasia with lower urinary tract symptoms and are commonly used in the United States in over-the-counter preparations. Saw palmetto berry is the most popular of these agents, and in vitro some studies suggest that liposterolic extract of the plant has antiandrogenic effects that inhibit the type 1 and type 2 isoenzymes of 5alpha-reductase; however there are no clinical studies that show any decrease in serum dihydrotestosterone or prostate-specific antigen. Its efficacy in the treatment of lower urinary tract symptoms has not been conclusively proven. Clinical efficacy was suggested by a meta-analysis of Permixon, a formulation of saw palmetto, but the meta-analysis was done on suboptimal studies. One trial supports the equivalency of Permixon to finasteride in treating moderate to severe symptoms of benign prostatic hyperplasia, with less decrease in sexual function. However, without a control/placebo arm, the actual efficacy of the agents cannot be determined. Other than occasional gastrointestinal upset, no other side effects have been reported.
Saw palmetto supplement use and prostate cancer risk.:Bonnar-Pizzorno RM, Littman AJ, Kestin M, White E.School of Nutrition and Exercise Science, Bastyr University, Kenmore, WA 98028-4966, USA.[PMID: 16965237]
Saw palmetto is an herb used to treat the symptoms of benign prostatic hyperplasia. In vitro studies have found that saw palmetto inhibits growth of prostatic cancer cells and may induce apoptosis. To evaluate whether saw palmetto supplements are associated with a reduced risk of prostate cancer, we conducted a prospective cohort study of 35,171 men aged 50-76 yr in western Washington state. Subjects completed questionnaires between 2000 and 2002 on frequency of use of saw palmetto supplements and saw palmetto-containing multivitamins over the previous 10 yr in addition to other information on supplement intake, medical history, and demographics. Men were followed through December 2003 (mean of 2.3 yr of follow-up) via the western Washington Surveillance, Epidemiology, and End Results cancer registry, during which time 580 developed prostate cancer. Ten percent of the cohort used saw palmetto at least once per week for a year in the 10 yr before baseline. No association was found between this level of use of saw palmetto and risk of prostate cancer development [hazard ratio (HR) = 0.95; 95% confidence interval = 0.74-1.23] or with increasing frequency or duration of use. In this free-living population, use of commercial saw palmetto, which varies widely in dose and constituent ratios, was not associated with prostate cancer risk.
Saw palmetto and lower urinary tract symptoms: what is the latest evidence?:Curr Urol Rep. 2006 Jul;7(4):260-5.Avins AL, Bent S. Northern California Kaiser-Permanente Division of Research, 2000 Broadway, 3rd Floor, Oakland, CA 94612, USA. avins@itsa.ucsf.edu.[PMID: 16930496]
The use of dietary supplements for treating a wide range of health conditions has grown rapidly in the United States. In the field of men's health, the most common dietary supplement used is an extract of the berry of the saw palmetto plant, with which men commonly self-medicate in order to treat lower urinary tract symptoms. Throughout the past two decades, substantial literature has emerged examining the biologic and clinical effects of saw palmetto extracts. Several lines of evidence suggest that saw palmetto may exert physiologic effects consistent with a beneficial clinical effect on the mechanisms of benign prostatic hyperplasia. Although most clinical studies tend to suggest a modest efficacy benefit of saw palmetto, more recent studies are less consistent and the precise clinical value of saw palmetto for treating lower urinary tract symptoms remains undefined. Overall, there appear to be few safety concerns with short-term use of this herbal medicine, although large-scale and longer-term safety studies have not been performed. Higher-quality studies are currently underway to better define the potential benefits and risks of plant-based extracts for treating symptoms related to benign prostatic hyperplasia.
Hepatotoxicity potential of Saw Palmetto (Serenoa repens) in rats.:Phytomedicine. 2007 Feb;14(2-3):204-8. Epub 2006 Jul 18.Singh YN, Devkota AK, Sneeden DC, Singh KK, Halaweish F.Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA.[PMID: 16854576]
Saw palmetto (Serenoa repens L.) is an herbal drug used to treat symptoms of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). There has been a report that a preparation containing this herb has caused cholestatic hepatitis in one person and some indications exist that it may have the potential to produce liver toxicity. The purpose of this study was to evaluate the effect of saw palmetto on rat liver function by measuring its effects on several enzymes and formation of malondialdehyde (MDA), a byproduct of lipid peroxidation. A significant increase in these parameters is considered an indication of liver toxicity. Thirty-six rats were divided into 6 groups of 6 animals each. They were treated for 2 or 4 weeks with a placebo or saw palmetto at doses of 9.14 or 22.86mg/kg/body wt./day; that is, 2x and 5x the maximum recommended daily human dosages. After 2 or 4 weeks, the animals were sacrificed and blood was collected to prepare serum for enzyme assays, which were performed using commercially available kits. A portion of the liver was removed, and a homogenate prepared for the lipid peroxidation assay. Results showed no significant difference in animal body weight, enzyme activity, or MDA formation at either time or dosage level, as compared to controls. The data indicate that at the doses and time periods tested, saw palmetto did not produce any significant effect on the normal biological markers of liver toxicity.
The efficacy of drugs for the treatment of LUTS/BPH, a study in 6 European countries.:Eur Urol. 2007 Jan;51(1):207-15; discussion 215-6. Epub 2006 Jun 27.Hutchison A, Farmer R, Verhamme K, Berges R, Navarrete RV.Postgraduate Medical School, University of Surrey, Guildford, UK. a.hutchison@surrey.ac.uk
OBJECTIVES: This paper profiles the usage and effectiveness of various LUTS/BPH drugs in real-life practice. METHOD: The TRIUMPH study recorded the treatment and outcomes of 2351 newly-presenting LUTS/BPH patients in 6 European countries over a 1-year follow-up period. At each visit the clinician recorded the treatment, co-morbidities, complications and drugs prescribed, and the patient completed an IPSS questionnaire. The results were analysed using change in IPSS as the primary outcome measure. RESULTS: Over the study period 74.9% of patients were prescribed medication, the majority (83% of those medicated) were prescribed only a single drug. Tamsulosin was the most commonly prescribed drug in all countries (38% of medicated cases), although with national variation from 24% in Poland to 70% in Italy. The alpha-blockers were the most effective, with a mean reduction of 6.3 IPSS points. Finasteride was slightly less effective (4.1 points). Significant improvements were seen in 43% of patients on phytotherapy with Serenoa repens or Pygeum africanum compared to 57% of those on finasteride and 68% on alpha-blockers. The only combination therapy found to produce a statistically significant improvement over the use of individual drugs was finasteride+tamsulosin (8.1 points compared to 6.7 for tamsulosin alone and 4.2 for finasteride alone). CONCLUSIONS: All drug treatments showed some improvement over watchful-waiting for most patients over the study period: the alpha-blockers were found to be the most effective. There were marked national differences in prescribing patterns, both in individual drug choice and in the use of combination therapies.
Saw palmetto-induced pancreatitis.:South Med J. 2006 Jun;99(6):611-2.Jibrin I, Erinle A, Saidi A, Aliyu ZY.St. Agnes Healthcare, 900 South Caton Avenue, Baltimore, MD 21229, USA. imjibrin@yahoo.com.[PMID: 16800417]
Saw palmetto is a frequently used botanical agent in benign prostatic enlargement (BPH). Although it has been reported to cause cholestatic hepatitis and many medical conditions, Saw palmetto has not been implicated in acute pancreatitis. We report a case of a probable Saw palmetto induced acute hepatitis and pancreatitis. A 55-year-old reformed alcoholic, sober for greater than 15 years, presented with severe non-radiating epigastric pain associated with nausea and vomiting. His only significant comorbidity is BPH for which he intermittently took Saw palmetto for about four years. Physical examination revealed normal vital signs, tender epigastrium without guarding or rebound tenderness. Cullen and Gray Turner signs were negative. Complete blood count and basic metabolic profile were normal. Additional laboratory values include a serum amylase: 2,152 mmol/L, lipase: 39,346 mmol/L, serum triglyceride: 38 mmol/L, AST: 1265, ALT: 1232 and alkaline phosphatase was 185. Abdominal ultrasound and magnetic resonance cholangiography revealed sludge without stones. A hepatic indole diacetic acid scan was negative. Patient responded clinically and biochemically to withdrawal of Saw palmetto. Two similar episodes of improvements followed by recurrence were noted with discontinuations and reinstitution of Saw Palmetto. Simultaneous and sustained response of hepatitis and pancreatitis to Saw palmetto abstinence with reoccurrence on reinstitution strongly favors drug effect. "Natural" medicinal preparations are therefore not necessarily safe and the importance of detailed medication history (including "supplements") cannot be over emphasized.
Effect of D-004, a lipid extract from the Cuban royal palm fruit, on atypical prostate hyperplasia induced by phenylephrine in rats.:Drugs R D. 2006;7(4):233-41.Arruzazabala ML, Mas R, Molina V, Noa M, Carbajal D, Mendoza N.Center of Natural Products, National Center for Scientific Research, Havana City, Cuba. clinica@enet.cu.[PMID: 16784248]
BACKGROUND AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that results in obstructive lower urinary tract symptoms. Saw palmetto (Serenoa repens), the dwarf American palm (Arecaceae family), is commonly used to treat BPH. The Cuban royal palm (Roystonea regia) also belongs to the Arecaceae family, and 200-400mg of D-004, a lipid extract from its fruits, administered orally for 14 days has been shown to prevent testosterone- but not dihydrotestosterone-induced prostatic hyperplasia in rats. D-004 (125-250 microg/mL) added to preparations of rat vas deferens caused a marked, dose-dependent and significant inhibition of noradrenaline-induced smooth muscle contraction, a response mediated through alpha(1)-adrenoceptors, and was more effective in these respects than Saw palmetto. However, the in vivo effects of D-004 and Saw palmetto on the hypertensive response induced by noradrenaline were modest (albeit significant), and neither treatment affected resting blood pressure or heart rate in rats. The differential effects of D-004 in in vitro and in vivo models could be related to a differential affinity for adrenoceptor subtypes or to different bioavailabilities in vascular and urogenital targets. Phenylephrine injected into rodents induces prostatic hyperplasia with all the characteristic morphological changes of the condition but does not result in enlargement of the prostate. Therefore, this phenylephrine-induced change in rat prostate tissue is called atypical prostatic hyperplasia. It serves as an in vivo model of prostatic hyperplasia induced by stimulation of alpha(1)-adrenoceptors. The objective of this study was to determine whether D-004 can inhibit induction of atypical prostatic hyperplasia by phenylephrine in rats. METHODS: Rats were randomly distributed into five groups (ten rats/group). One group was a negative control and received oral vehicle only. The other four groups were injected subcutaneously with phenylephrine (2 mg/kg): of these groups, one was a positive control receiving the vehicle, and the other three groups were treated with D-004 or Saw palmetto (both 400 mg/kg) or tamsulosin 0.4 mg/kg. All active treatments were given orally for 28 days. After completion of treatment, rats were placed unrestrained in metabolic cages and micturition studies were performed. The rats were later killed and their prostates removed and weighed. Prostate samples were processed for histological study, with histological changes being assessed according to a scoring system. Bodyweight was measured at baseline and at weekly intervals. RESULTS: Histological examination of positive control rats revealed features of atypical prostatic hyperplasia, with piling-up, papillary and cribiform patterns and budding-out of epithelial cells. Micturition assessment revealed that phenylephrine significantly lowered both the total volume of urine in 1 hour and the volume per micturition; the latter was considered the main efficacy variable. D-004 and Saw palmetto extracts significantly prevented this reduction in volume per micturition by 70.5% and 68.6%, respectively, while tamsulosin totally abolished the reduction in micturition induced by phenylephrine (100% inhibition). Tamsulosin, D-004 and Saw palmetto significantly reduced the histological changes of atypical prostatic hyperplasia induced by phenylephrine by 73.1%, 61.2% and 50.0%, respectively. CONCLUSIONS: Administration of D-004 resulted in marked and significant prevention of phenylephrine-induced impairment of micturition and histological changes in rat prostate. These findings indicate that, in vivo, D-004 effectively opposes these responses to phenylephrine, which are mediated through urogenital alpha(1)-adrenoceptors. In this respect, D-004 was moderately more effective than Saw palmetto, a phytotherapeutic standard used to treat BPH, but less effective than tamsulosin, a selective alpha(1A)-adrenoceptor antagonist.
Extracts from Pygeum africanum and other ethnobotanical species with antiandrogenic activity.:Planta Med. 2006 Jul;72(9):807-13. Epub 2006 Jun 19.Schleich S, Papaioannou M, Baniahmad A, Matusch R. Institut fur Pharmazeutische Chemie, Philipps-Universitat Marburg, Marburg, Germany.[PMID: 16783690]
Extracts from Pygeum africanum, Serenoa repens and Cucurbita pepo are used in the treatment of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The activity of the androgen receptor (AR) is known to control growth of the prostate. Here, we examined extracts of these plants for their antiandrogenic activity using an AR responsive reporter gene assay for drug discovery. A selective dichloromethane extract from the stem barks of Pygeum africanum revealed the highest antiandrogenic effect. Bioactivity-directed fractionation of this extract led to the isolation of N-butylbenzenesulfonamide (NBBS) indicating that extracts of the stem bark of P. africanum harbour androgen antagonistic activity. This compound may provide a novel approach for the prevention and treatment of BPH and human PCa.
Herbal medicine: the science of the art.:Proc Nutr Soc. 2006 May;65(2):145-52.Walker AF.Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, University of Reading, Reading RG6 6AP, UK. a.f.walker@reading.ac.uk.[PMID: 16672075 ]
In the last 50 years science has provided new perspectives on the ancient art of herbal medicine. The present article discusses ways in which the evidence base for the professional use of 'Western' herbal medicine, as therapy to treat disease, known as phytotherapy, can be strengthened and developed. The evidence base for phytotherapy is small and lags behind that for the nutritional sciences, mainly because phytochemicals are ingested as complex mixtures that are incompletely characterised and have only relatively recently been subject to scientific scrutiny. While some methodologies developed for the nutritional sciences can inform phytotherapy research, opportunities for observational studies are more limited, although greater use could be made of patient case notes. Randomised clinical trials of single-herb interventions are relatively easy to undertake and increasing numbers of such studies are being published. Indeed, enough data are available on three herbs (ginkgo (Ginkgo biloba), St John's wort (Hypericum perforatum) and saw palmetto (Serenoa repens)) for meta-analyses to have been undertaken. However, phytotherapy is holistic therapy, using lifestyle advice, nutrition and individually-prescribed mixtures of herbs aimed at reinstating homeostasis. While clinical experience shows that this approach is applicable to a wide range of conditions, including chronic disease, evidence of its efficacy is scarce. Strategies for investigating the full holistic approach of phytotherapy and its main elements are discussed and illustrated through the author's studies at the University of Reading.
Efficacy and safety of a combination of sabal and urtica extract in lower urinary tract symptoms. A randomized, double-blind study versus tamsulosin.:Arzneimittelforschung. 2006;56(3):222-9.Engelmann U, Walther C, Bondarenko B, Funk P, Schlafke S. Department of Urology, University Clinics of Cologne, Cologne, Germany.[PMID: 16618015]
The aim of this prospective, randomized, double-blind, double-dummy, multicenter clinical trial was to investigate the efficacy and safety of PRO 160/120 (Prostagutt forte), a fixed combination preparation of 160 mg Sabal fruit extract WS 1473 and 120 mg Urtica root extract WS 1031 per capsule, in comparison to the alpha1-adrenoceptor antagonist tamsulosin (CAS 106463-17-6) in lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). 140 elderly out-patients suffering from LUTS caused by BPH, with an initial score > or = 13 points in the International Prostate Symptom Score (I-PSS), received 2 x 1 capsule/d PRO 160/120 or 1 x 0.4 mg/d tamsulosin and were treated for 60 weeks with interim visits at weeks 8, 16, 24, 36, and 48. The primary outcome measure for efficacy was the change in I-PSS total score, the percentage of patients with an I-PSS score < or = 7 points at endpoint ('responders') was analyzed as well. During 60 weeks of randomized treatment the I-PSS total score was reduced by a median of 9 points in both groups. In total, 32.4 % of the patients in the PRO 160/120 group and 27.9% in the tamsulosin group were responders (test for non-inferiority of PRO 160/120: p = 0.034; non-inferiority margin 10%). Both drugs were well tolerated, with one adverse event in 1514 treatment days for PRO 160/120 and one event in 1164 days for tamsulosin. The study supports non-inferiority of PRO 160/120 in comparison to tamsulosin in the treatment of LUTS caused by BPH.
Analysis of the interactions of botanical extract combinations against the viability of prostate cancer cell lines.:Evid Based Complement Alternat Med. 2006 Mar;3(1):117-24.Adams LS, Seeram NP, Hardy ML, Carpenter C, Heber D. Center for Human Nutrition, David Geffen School of Medicine, University of California at Los Angeles, 90095-1742, USA. ladams@mednet.ucla.edu.[PMID: 16550232]
Herbal medicines are often combinations of botanical extracts that are assumed to have additive or synergistic effects. The purpose of this investigation was to compare the effect of individual botanical extracts with combinations of extracts on prostate cell viability. We then modeled the interactions between botanical extracts in combination isobolographically. Scutellaria baicalensis, Rabdosia rubescens, Panax-pseudo ginseng, Dendranthema morifolium, Glycyrrhiza uralensis and Serenoa repens were collected, taxonomically identified and extracts prepared. Effects of the extracts on cell viability were quantitated in prostate cell lines using a luminescent ATP cell viability assay. Combinations of two botanical extracts of the four most active extracts were tested in the 22Rv1 cell line and their interactions assessed using isobolographic analysis. Each extract significantly inhibited the proliferation of prostate cell lines in a time- and dose-dependent manner except S. repens. The most active extracts, S. baicalensis, D. morifolium, G. uralensis and R. rubescens were tested as two-extract combinations. S. baicalensis and D. morifolium when combined were additive with a trend toward synergy, whereas D. morifolium and R. rubescens together were additive. The remaining two-extract combinations showed antagonism. The four extracts together were significantly more effective than the two-by-two combinations and the individual extracts alone. Combining the four herbal extracts significantly enhanced their activity in the cell lines tested compared with extracts alone. The less predictable nature of the two-way combinations suggests a need for careful characterization of the effects of each individual herb based on their intended use.
Determination of campesterol, stigmasterol, and beta-sitosterol in saw palmetto raw materials and dietary supplements by gas chromatography: single-laboratory validation.:J AOAC Int. 2006 Jan-Feb;89(1):22-34.Sorenson WR, Sullivan D.Covance Laboratories, 3301 Kinsman Blvd, Madison, WI 53704, USA. wendy.sorenson@covance.com.[PMID:16512224]
In conjunction with an AOAC Presidential Task Force on Dietary Supplements, a method was validated for measurement of 3 plant sterols (phytosterols) in saw palmetto raw materials, extracts, and dietary supplements. AOAC Official Method 994.10, "Cholesterol in Foods," was modified for purposes of this validation. Test samples were saponified at high temperature with ethanolic potassium hydroxide solution. The unsaponifiable fraction containing phytosterols (campesterol, stigmasterol, and beta-sitosterol) was extracted with toluene. Phytosterols were derivatized to trimethylsilyl ethers and then quantified by gas chromatography with a hydrogen flame ionization detector. The presence of the phytosterols was detected at concentrations greater than or equal to 1.00 mg/100 g based on 2-3 g of sample. The standard curve range for this assay was 0.00250 to 0.200 mg/mL. The calibration curves for all phytosterols had correlation coefficients greater than or equal to 0.995. Precision studies produced relative standard deviation values of 1.52 to 7.27% for campesterol, 1.62 to 6.48% for stigmasterol, and 1.39 to 10.5% for beta-sitosterol. Recoveries for samples fortified at 100% of the inherent values averaged 98.5 to 105% for campesterol, 95.0 to 108% for stigmasterol, and 85.0 to 103% for beta-sitosterol.
Saw palmetto for benign prostatic hyperplasia.:N Engl J Med. 2006 Feb 9;354(6):557-66.Bent S, Kane C, Shinohara K, Neuhaus J, Hudes ES, Goldberg H, Avins AL. Osher Center for Integrative Medicine, Department of Medicine, University of California, San Francisco, San Francisco, USA. bent@itsa.ucsf.edu.[PMID: 16467543]
BACKGROUND: Saw palmetto is used by over 2 million men in the United States for the treatment of benign prostatic hyperplasia and is commonly recommended as an alternative to drugs approved by the Food and Drug Administration. METHODS: In this double-blind trial, we randomly assigned 225 men over the age of 49 years who had moderate-to-severe symptoms of benign prostatic hyperplasia to one year of treatment with saw palmetto extract (160 mg twice a day) or placebo. The primary outcome measures were changes in the scores on the American Urological Association Symptom Index (AUASI) and the maximal urinary flow rate. Secondary outcome measures included changes in prostate size, residual urinary volume after voiding, quality of life, laboratory values, and the rate of reported adverse effects. RESULTS: There was no significant difference between the saw palmetto and placebo groups in the change in AUASI scores (mean difference, 0.04 point; 95 percent confidence interval, -0.93 to 1.01), maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, -0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels during the one-year study. The incidence of side effects was similar in the two groups. CONCLUSIONS: In this study, saw palmetto did not improve symptoms or objective measures of benign prostatic hyperplasia. (ClinicalTrials.gov number, NCT00037154.).
The overlapping lower urinary tract symptoms of benign prostatic hyperplasia and prostatitis.:Curr Opin Urol. 2006 Jan;16(1):5-10.Nickel JC.Department of Urology, Queen's University, Kingston, Ontario, Canada. jcn@post.queensu.ca.[PMID:16385194]
PURPOSE OF REVIEW: To investigate the relationship, diagnosis and treatment of the overlapping lower urinary tract symptoms experienced by men diagnosed with benign prostatic hyperplasia and prostatitis. RECENT FINDINGS: Recent studies have clearly shown that men can suffer from both benign prostatic hyperplasia and prostatitis. Approximately 5-20% of men diagnosed with benign prostatic hyperplasia suffer from prostatitis-like symptoms, while over one third of men diagnosed with benign prostatic hyperplasia have had a diagnosis of prostatitis in the past. Differentiation between these two symptom-based medical conditions can be difficult because of overlapping symptoms, but pain clearly identifies those patients with chronic prostatitis. Treatment for men with co-occurring benign prostatic hyperplasia and prostatitis may include alpha-blockers, 5alpha-reductase inhibitors and phytotherapies (saw palmetto and bee pollen extract), with evidence clearly showing the benefits of alpha-blocker therapy. SUMMARY: Benign prostatic hyperplasia and chronic prostatitis are a common cause of lower urinary tract symptoms and frequently co-occur in older men. The best treatment for men with lower urinary tract symptoms associated with both benign prostatic hyperplasia and prostatitis is alpha-blockers.
Total and specific complementary and alternative medicine use in a large cohort of men with prostate cancer.:Urology. 2005 Dec;66(6):1223-8.Chan JM, Elkin EP, Silva SJ, Broering JM, Latini DM, Carroll PR.Department of Urology, University of California-San Francisco, California 94143-1695, USA. june@uorg.ucsf.edu.[PMID: 16360447]
OBJECTIVES: To assess specific complementary and alternative medicine (CAM) use in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a large, community-based national registry of men with prostate cancer. METHODS: We examined more than 50 types of CAM use in a large, national, community-based registry of men with prostate cancer (CaPSURE). Participants completed biannual surveys within 2 years of diagnosis and treatment. We analyzed associations of CAM use with sociodemographic and clinical features, using chi-square tests and multivariate logistic regression. RESULTS: One third of 2582 respondents reported using CAM. Common practices included vitamin and mineral supplements (26%), herbs (16%), antioxidants (13%), and CAM for prostate health (12%; eg, saw palmetto, selenium, vitamin E, lycopene). In multivariate analyses, users were more likely to have other comorbid conditions, worse cancer grade at diagnosis, higher incomes, more education, and to live in the West. CONCLUSIONS: Complementary and alternative medicine use was associated with sociodemographic and clinical characteristics in this large sample of men with prostate cancer. These results should be considered by health care professionals counseling men with prostate cancer regarding diet and secondary prevention.
Herb-drug interactions. Interactions between saw palmetto and prescription medications.:Geriatrics. 2005 Nov;60(11):32, 34.Bressler R.University of Arizona Health Sciences Center and the Sarver Heart Center, Tucson, USA.[PMID:16287339]
Patients over age 50 typically present with one chronic disease per decade. Each chronic disease typically requires long-term drug therapy, meaning most older patients require several drugs to maintain health. Simultaneously, use of complementary and alternative medicine (CAM) has increased in the United States in the last 20 years, reaching 36% in 2002; herbal medicine use accounts for approximately 22% of all CAM use. Older adults often add herbal medicines to prescription medications, yet do not always inform their physicians. The drug metabolizing enzyme systems process all compounds foreign to the body, including prescription and herbal medications. Therefore use of both medicinals simultaneously has a potential for adverse interactions. This review, which discusses saw palmetto, is the last in a series covering the documented interactions among the top 5 efficacious herbal medicines and prescription drugs.
Efficacy of a combined Sabal-urtica preparation in the symptomatic treatment of benign prostatic hyperplasia. Results of a placebo-controlled double-blind study:MMW Fortschr Med. 2005 Oct 6;147 Suppl 3:103-8.Popa G, Hagele-Kaddour H, Walther C. Facharzt fur Urologie, Ludwigshafen.[PMID:16261945]
This re-evaluation of a double-blind placebo-controlled therapeutic study of the combined sabal-urtica preparation PRO 160/120 investigates the changes in the irritative symptoms of benign prostatic hyperplasia (BPH) under the test substance in comparison with placebo. It was found that, over the study period of 24 weeks, the micturition symptoms frequency and urgency were statistically significantly improved under the well-tolerated PRO 160/120 in comparison with placebo. The patient's quality of life was also significantly better under PRO 160/120 in comparison with placebo. CONCLUSION: The often distressing symptoms of BPH can be effectively ameliorated already after only a few weeks of treatment with the sabal-urtica preparation PRO 160/120. In particular those patients with the stigmatizing symptoms urinary urgency and frequency benefit from such treatment.
Saw palmetto is an indirectly acting sympathomimetic in the rat-isolated prostate gland.:Prostate. 2006 Feb 1;66(2):115-23.Cao N, Haynes JM, Ventura S.Prostate Research Co-Operative, Faculty of Pharmacy, Monash University, Parkville, Victoria, Australia.[PMID: 16114061 ]
BACKGROUND: To investigate whether saw palmetto that inhibits alpha1-adrenoceptor binding in vitro affects contractility of the rat prostate gland. METHODS: The effects of a commercially available saw palmetto extract were examined on the contractility of rat-isolated prostate glands. The extract was tested in the presence and absence of phentolamine, prazosin, yohimbine, propranolol, hexamethonium, cocaine, desipramine, nifedipine, guanethidine, atropine, and alpha,beta-methylene ATP to evaluate the mechanism of action. Isolated preparations of rat vas deferens and bladder were used for comparison. RESULTS: Unexpectedly, saw palmetto extract caused contractions of the rat prostate gland that could be attenuated by prazosin, phentolamine, nifedipine, guanethidine, cocaine, and desipramine but not by any of the other pharmacological tools. Similar contractile effects were observed in rat-isolated vas deferens preparations but not in rat-isolated bladder preparations. CONCLUSIONS: In the rat prostate gland, saw palmetto extract causes indirect alpha1-adrenoceptor-mediated contractions via the release of noradrenaline from sympathetic neurons.
A preliminary investigation of the enzymatic inhibition of 5alpha-reduction and growth of prostatic carcinoma cell line LNCap-FGC by natural astaxanthin and Saw Palmetto lipid extract in vitro.:J Herb Pharmacother. 2005;5(1):17-26.Anderson ML.Research and Development, Triarco Industries, Wayne, NJ 07470, USA. mark.anderson@triarco.com.[PMID: 16093232]
Inhibition of 5alpha-reductase has been reported to decrease the symptoms of benign prostate hyperplasia (BPH) and possibly inhibit or help treat prostate cancer. Saw Palmetto berry lipid extract (SPLE) is reported to inhibit 5alpha-reductase and decrease the clinical symptoms of BPH. Epidemiologic studies report that carotenoids such as lycopene may inhibit prostate cancer. In this investigation the effect of the carotenoid astaxanthin, and SPLE were examined for their effect on 5alpha-reductase inhibition as well as the growth of prostatic carcinoma cells in vitro. These studies support patent #6,277,417 B1. The results show astaxanthin demonstrated 98% inhibition of 5alpha-reductase at 300 microg/mL in vitro. Alphastat, the combination of astaxanthin and SPLE, showed a 20% greater inhibition of 5alpha-reductase than SPLE alone n vitro. A nine day treatment of prostatic carcinoma cells with astaxanthin in vitro produced a 24% decrease in growth at 0.1 mcg/mL and a 38% decrease at 0.01 mcg/mL. SPLE showed a 34% decrease at 0.1 mcg/mL. CONCLUSIONS: Low levels of carotenoid astaxanthin inhibit 5alpha-reductase and decrease the growth of human prostatic cancer cells in vitro. Astaxanthin added to SPLE shows greater inhibition of 5alpha-reductase than SPLE alone in vitro.
Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9.: J Altern Complement Med. 2005 Jun;11(3):433-9.Yale SH, Glurich I.Department of Internal Medicine, Marshfield Clinic, Marshfield, WI 54449, USA. yale.steven@mcrf.mfldclin.edu.[PMID: 15992226]
OBJECTIVE: To study the potential of three top-selling herbal products, Ginkgo biloba, Echinacea purpurea, and Serenoa repens to inhibit the in vitro enzymatic activity of three of the most important drug metabolizing enzymes, cytochrome P450 (CYP) 3A4, 2D6, and 2C9. METHODS: High throughput CYP inhibition screening was used to test the inhibitory capacity of extracts of commercially available herbal medications on the metabolism of CYP enzyme substrates. RESULTS: S. repens showed potent inhibition of the metabolic activity of all three CYPs tested. The effects of G. biloba and E. purpurea varied. E. purpurea demonstrated mild inhibition of CYP3A4 activity with 7- benzyloxy-4-trifluoromethylcoumarin (BFC) as the model substrate, but mild inducing effects in the presence of the model substrate resorufin benzyl ether (BzRes). Little effect on CYP2D6 and moderate inhibition of CYP2C9 was seen with both E. purpurea and G. biloba. G. biloba also showed mild-to-moderate inhibition of CYP3A4 depending on the model substrate. CONCLUSIONS: The inhibitory capacity of herbal products varies depending on the concentrations of the model substrate and the herbal extract, as well as the identity of the model substrate, as demonstrated by the varied effects of CYP3A4 enzymatic activity with different model substrates. The potential for strong adverse interactions exists for Serenoa repens, which was a potent inhibitor of all three CYPs examined. Physicians are encouraged to advise patients of the risks of combining herbal products with prescription medications.
Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms--a placebo-controlled, double-blind, multicenter trial.:World J Urol. 2005 Jun;23(2):139-46. Epub 2005 Jun 1.Lopatkin N, Sivkov A, Walther C, Schlafke S, Medvedev A, Avdeichuk J, Golubev G, Melnik K, Elenberger N, Engelmann U.Institute of Urology, 3rd Parkovaya Street 51, 105425 Moscow, Russia.[PMID: 15928959]
The efficacy and tolerability of a fixed combination of 160 mg sabal fruit extract WS 1473 and 120 mg urtica root extract WS 1031 per capsule (PRO 160/120) was investigated in elderly, male patients suffering from lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia in a prospective multicenter trial. A total of 257 patients (129 and 128, respectively) were randomized to treatment with PRO 160/120 or placebo (127 and 126 were evaluable for efficacy). Following a single-blind placebo run-in phase of 2 weeks, the patients received 2 x 1 capsule/day of the study medication under double-blind conditions over a period of 24 weeks. Double-blind treatment was followed by an open control period of 24 weeks during which all patients were administered PRO 160/120. Outcome measures for treatment efficacy included the assessment of the patients' LUTS by means of the I-PSS self-rating questionnaire and a quality of life index as well as uroflow and sonographic parameters. Using the International Prostate Symptom Score (I-PSS), patients treated with PRO 160/120 exhibited a substantially higher total score reduction after 24 weeks of double-blind treatment than patients of the placebo group (6 points vs 4 points; P=0.003, one tailed) with a tendency in the same direction after 16 weeks. This applied to obstructive as well as to irritative symptoms, and to patients with moderate or severe symptoms at baseline. Patients randomized to placebo showed a marked improvement in LUTS (as measured by the I-PSS) after being switched to PRO 160/120 during the control period (P=0.01, one tailed, in comparison to those who had been treated with PRO 160/120 in the double-blind phase). The tolerability of PRO 160/120 was comparable to the placebo. In conclusion, PRO 160/120 was clearly superior to the placebo for the amelioration of LUTS as measured by the I-PSS. PRO 160/120 is advantageous in obstructive and irritative urinary symptoms and in patients with moderate and severe symptoms. The tolerability of the herbal extract was excellent.
Serenoa repens treatment modifies bax/bcl-2 index expression and caspase-3 activity in prostatic tissue from patients with benign prostatic hyperplasia.:J Urol. 2005 Feb;173(2):507-10.Vela-Navarrete R, Escribano-Burgos M, Farre AL, Garcia-Cardoso J, Manzarbeitia F, Carrasco C.Department of Urology, Fundacion Jimenez Diaz, Autonomous University of Madrid, Madrid, Spain.[PMID: 15643230]
PURPOSE: Permixon is a lipidosterolic extract of Serenoa repens (SR) widely used to treat men with benign prostatic hyperplasia (BPH). We tested the effect of this drug on molecular mechanisms associated with apoptosis, such as the Bax-to-Bcl-2 expression ratio and caspase-3 activity, in prostatic tissue from men with symptomatic BPH treated for 3 months before surgery. MATERIALS AND METHODS: An open, multicenter pilot study of 2 parallel groups of patients with BPH was done. They were randomized to be followed for 3 weeks without any treatment before surgery (control group) or to receive 160 mg SR orally twice daily for a 3-month period preceding the same surgery. Surgery was ultimately performed in 17 controls and 12 patients by transurethral prostate resection or retropubic adenomectomy. Bax and Bcl-2 expression, and caspase-3 activity were determined by Western blot in 15 controls and 10 patients, and reported in blinded fashion. RESULTS: The Bax-to-Bcl-2 ratio, which is used as an apoptotic index, was significantly increased in the prostatic tissue of treated patients. The level of the intact 116 kDa poly (adenosine diphosphate-ribose) polymerase form, an enzyme involved in the cell death apoptotic pathway, was also found to be decreased in prostatic tissue from SR treated patients, suggesting increased caspase 3 activity in the prostate. CONCLUSIONS: Permixon increased molecular markers involved in the apoptotic process, ie the Bax-to-Bcl-2 expression ratio and caspase-3 activity. This could have clinical relevance due to the improvement in symptoms produced by treatment with this drug.
Intake of selected nutritional supplements by African-American men.:Urology. 2004 Dec;64(6):1094-7.Weinrich SP, Hudson Priest J, Moyad MA, Weinrich MC. School of Nursing, University of Louisville, Louisville, Kentucky 40292 , USA.
OBJECTIVES: To measure the self-reported intake of vitamins, selenium, vitamin E, and saw palmetto supplements in African-American men. METHODS: A correlational study was conducted of 198 African-American men, aged 40 to 70 years old, who attended a community-based free prostate cancer educational and screening program. The rates of supplement use were compared among demographic groups. RESULTS: Just more than one half of the men (51%) took one or more of the supplements. Almost one half (46%) took multivitamin supplements. About 34% took vitamin E supplements, 6% took selenium supplements, and 7% took saw palmetto. Higher income men were more likely to take nutritional supplements. No statistically significant associations were found between supplement use and age, education, or marital status. Almost all use of selenium, vitamin E, and saw palmetto was among men who were already taking a multivitamin supplement. CONCLUSIONS: The implications from the results of this study include the need to conduct an assessment of supplement intake as part of the health history.
Serenoa repens (Permixon) inhibits the 5alpha-reductase activity of human prostate cancer cell lines without interfering with PSA expression.:Int J Cancer. 2005 Mar 20;114(2):190-4.[PMID: 15543614]Habib FK, Ross M, Ho CK, Lyons V, Chapman K.Prostate Research Group, University of Edinburgh, School of Molecular and Clinical Medicine, 2nd Floor Main Outpatient Building, Western General Hospital, Edinburgh EH2 2XU, Scotland, UK.
The phytotherapeutic agent Serenoa repens is an effective dual inhibitor of 5alpha-reductase isoenzyme activity in the prostate. Unlike other 5alpha-reductase inhibitors, Serenoa repens induces its effects without interfering with the cellular capacity to secrete PSA. Here, we focussed on the possible pathways that might differentiate the action of Permixon from that of synthetic 5alpha-reductase inhibitors. We demonstrate that Serenoa repens, unlike other 5alpha-reductase inhibitors, does not inhibit binding between activated AR and the steroid receptor-binding consensus in the promoter region of the PSA gene. This was shown by a combination of techniques: assessment of the effect of Permixon on androgen action in the LNCaP prostate cancer cell line revealed no suppression of AR and maintenance of PSA protein expression at control levels. This was consistent with reporter gene experiments showing that Permixon failed to interfere with AR-mediated transcriptional activation of PSA and that both testosterone and DHT were equally effective at maintaining this activity. Our results demonstrate that despite Serenoa repens effective inhibition of 5alpha-reductase activity in the prostate, it did not suppress PSA secretion. Therefore, we confirm the therapeutic advantage of Serenoa repens over other 5alpha-reductase inhibitors as treatment with the phytotherapeutic agent will permit the continuous use of PSA measurements as a useful biomarker for prostate cancer screening and for evaluating tumour progression.
Is there a scientific basis for the therapeutic effects of serenoa repens in benign prostatic hyperplasia? Mechanisms of action.:J Urol. 2004 Nov;172(5 Pt 1):1792-9.Buck AC.Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom. a-colinbuck@supanet.com.[PMID: 15540722]
PURPOSE: The huge resurgence of interest in herbal remedies has spawned a global industry that now competes with conventional drugs as adjuncts and/or alternatives for various conditions. The medical treatment of benign prostatic hyperplasia (BPH) is no exception. Along with alpha-blockers and 5alpha-reductase inhibitors the extract of the American dwarf palm, Serenoa repens, is unquestionably the most widely used. Together with Pygeum africanum, an extract from the bark of the African plum tree, it is licensed in Germany, France and other European countries for symptomatic BPH. This review was done to analyze the large number of in vivo and in vitro laboratory studies that have been performed with extracts of Serenoa repens to elucidate mechanism(s) of action. MATERIALS AND METHODS: A literature search (MEDLINE) revealed more than 30 publications relating to laboratory studies with extracts of Serenoa repens, addressing the question of a mechanism of action. It would appear that the n-hexane lipidosterolic extract of Serenoa repens, namely Permixon (Pierre Fabre Medicament, Boulogne, France), is a product that has uniquely been subjected to more scientific investigation than any other such preparation. RESULTS: Placebo controlled and comparative clinical studies of Permixon indicate its efficacy for BPH/lower urinary tract symptoms. Numerous mechanisms of action have been proposed, including an antiandrogenic action, an anti-inflammatory effect and an antiproliferative influence through the inhibition of growth factors. CONCLUSIONS: Set against the background of our current knowledge of the pathophysiology of the aging prostate, the results of these studies suggest a wide spectrum of activity. However, precise mechanism(s) of action remain obscure. Balance and caution are needed when extrapolating the results of in vitro laboratory studies to the complex human situation.
Efficacy of pretreatment with Serenoa repens on bleeding associated with transurethral resection of prostate.:Minerva Urol Nefrol. 2004 Mar;56(1):73-8.Pecoraro S, Annecchiarico A, Gambardella MC, Sepe G.Reparto di Alta Specialita Nefro-Urologico, Clinica Malzoni, Avellino. uropec@tin.it.[PMID: 15195032]
AIM: Aim of the study is to evaluate the efficacy of a pretreatment with lipidic-sterolic extract of Serenoa repens (Permixon) to reduce bleeding during transurethral resection of prostate (TURP) in patients with benign prostatic hyperplasia. METHODS: This is a monocentric, randomised versus control group study. We enrolled 108 patients, randomised either in the experimental group or in the control one. Patients in the experimental group received a pretreatment with Serenoa repens (320 mg/die of Permixon) for at least 8 weeks before the TURP procedure. In the control group patients did not receive any medical treatment before the intervention. RESULTS: Out of 108 enrolled patients, 88 were evaluated per protocol. In the pretreated group the perioperative bleeding was significantly lower than in the control one (respectively 124 vs 287 ml) and the need of transfusion decreased remarkably. Moreover, in the pretreated group, the duration of postoperative catheterization (respectively 3 vs 5 days) and the evaluated hematological parameters (red cells 4.5 vs 4 million, hemoglobin 13.4 vs 11.9 g, hematocrit 40% vs 35%) were significantly lower than in the control group. CONCLUSION: The pretreatment with Serenoa repens, before TURP procedure, improves the efficacy of the procedure itself and reduces the risk of complications, in particular perioperative bleeding and duration of postoperative catheterization.
Updated meta-analysis of clinical trials of Serenoa repens extract in the treatment of symptomatic benign prostatic hyperplasia.:BJU Int. 2004 Apr;93(6):751-6.Boyle P, Robertson C, Lowe F, Roehrborn C.Department of Epidemiology and Biostatistics, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy. director@iarc.fr.[PMID: 15049985]
OBJECTIVES: To determine, by analysing all available clinical trial data, the clinical efficacy against placebo of an extract from the fruit of the American dwarf palm tree, Serenoa repens (Permixon, Pierre Fabre Medicament, Castres, France), as there is controversy about the use of phytotherapeutic agents in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). METHODS: All clinical trial data published on Permixon, comprising 14 randomized clinical trials and three open-label trials, involving 4280 patients, were analysed. These trials were of different size (22-1100 patients) and duration (21-720 days). The peak urinary flow rate and nocturia were the two common endpoints. The statistical analysis was based on a random-effects meta-analysis. RESULTS: Permixon was associated with a mean (sem) reduction in the International Prostate Symptom Score (IPSS) of 4.78 (0.41). The mean placebo effect on peak urinary flow rate was an increase of 1.20 (0.49) mL/s. The estimated effect of Permixon was a further increase of 1.02 (0.50) mL/s (P = 0.042). Placebo was associated with a reduction in the mean number of nocturnal voids of 0.63 (0.14); there was a further reduction attributable to Permixon of 0.38 (0.07) (P < 0.001). There was some heterogeneity among the studies for nocturia; one over 2 years involving 396 patients and showing no difference between placebo and Permixon had a large effect on the results. CONCLUSIONS: This meta-analysis of all available published trials of Permixon for treating men with BPH showed a significant improvement in peak flow rate and reduction in nocturia above placebo, and a 5-point reduction in the IPSS.
Serenoa repens extract for benign prostate hyperplasia: a randomized controlled trial.:BJU Int. 2003 Aug;92(3):267-70.Willetts KE, Clements MS, Champion S, Ehsman S, Eden JA. Natural Therapies Unit, Royal Hospital for Women, Randwick, Australia.[PMID: 12887481]
OBJECTIVE: To compare the effect of a Serenoa repens extract with placebo for symptoms of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: In a double-blind placebo-controlled randomized trial between January 1999 and March 2000, 100 men with symptoms of BPH, aged < 80 years, with a maximum urinary flow rate of 5-15 mL/s for a voiding volume of 150 mL, were randomly and equally allocated to 320 mg S. repens extract or placebo (paraffin oil). The main outcome measures were the International Prostate Symptom Score (IPSS), peak urinary flow rate, and the Rosen International Index of Erectile Function (IIEF) questionnaire. RESULTS: There was no significant difference between the treatments over the 12 weeks of the study in the IPSS, peak urinary flow rate or for the IIEF questionnaire. CONCLUSIONS: During the trial all participants had some improvement in their symptoms of BPH but there was no significant beneficial effect of this S. repens extract over placebo in this 12-week trial.
A review of plant-derived and herbal approaches to the treatment of sexual dysfunctions.:J Sex Marital Ther. 2003 May-Jun;29(3):185-205.Rowland DL, Tai W. Department of Psychology, Valparaiso University, Valparaiso, Indiana 46383, USA. david.rowland@valpo.edu.[PMID: 12851124]
Despite the increasing availability of effective conventional medical treatments, plant-derived and herbal remedies continue to provide a popular alternative for men and women seeking to improve their sex life. Nevertheless, the efficacy of most herbal agents in treating sexual problems remains uncertain. Therapists and consumers alike would benefit from an increased understanding of commonly used herbal agents on the market, their purported or supported effects, and their potential side effects. To this end, we cataloged the major prosexual herbal agents currently sold in several representative health food stores. We also specify the sexual problem purportedly ameliorated by each herbal agent. Finally, we evaluate eight herbal agents commonly promoted for the treatment of sexual problems. This evaluation includes a review of the research supporting the use, efficacy, dose, adverse effects, contraindications, and possible mechanism of action of each. We conclude by commenting on the quality of current research, pointing out gaps in our knowledge, and noting the need for rigorous research and product control to adequately address questions regarding the efficacy of these agents.
"Bust enhancing" herbal products.:Obstet Gynecol. 2003 Jun;101(6):1345-9.Fugh-Berman A.Department of Health Care Sciences, George Washington University School of Medicine, Washington, DC, USA. fughberman@aol.com.[PMID: 12798545]
"Bust enhancing" herbal products are widely advertised. No clinical trials have been published. These products contain a variety of ingredients, including grains, hops, saw palmetto, dong quai, chaste-tree berry, wild yam, kava, fennel, black cohosh, and fenugreek. Several of these herbs are hormonally active; for example, hops contain 8-prenylnaringenin, a phytoestrogen that is more potent than other dietary phytoestrogens. Many bust-enhancing dietary supplements contain substrates for Fusarium, a fungus that produces zearalenone, a potent estrogen that has been associated with breast enlargement in humans and other species. The use of bust-enhancing products should be discouraged because of lack of evidence for efficacy and long-term safety concerns.
Inhibition of type 1 and type 2 5alpha-reductase activity by free fatty acids, active ingredients of Permixon.:J Steroid Biochem Mol Biol. 2002 Oct;82(2-3):233-9.Raynaud JP, Cousse H, Martin PM. D.R.I.T.T., Universite Pierre et Marie Curie, 4 Place Jussieu, Paris, France. jean-pierre.raynaud@admp6.jussieu.fr.[PMID: 12477490]
In different cell systems, the lipido-sterolic extract of Serenoa repens (LSESr, Permixon inhibits both type 1 and type 2 5alpha-reductase activity (5alphaR1 and 5alphaR2). LSESr is mainly constituted of fatty acids (90+/-5%) essentially as free fatty acids (80%). Among these free fatty acids, the main components are oleic and lauric acids which represent 65% and linoleic and myristic acids 15%.To evaluate the inhibitory effect of the different components of LSESr on 5alphaR1 or 5alphaR2 activity, the corresponding type 1 and type 2 human genes have been cloned and expressed in the baculovirus-directed insect cell expression system Sf9. The cells were incubated at pH 5.5 (5alphaR2) and pH 7.4 (5alphaR1) with 1 or 3nM testosterone in presence or absence of various concentrations of LSESr or of its different components. Dihydrotestosterone formation was measured with an automatic system combining HPLC and an on-line radiodetector.The inhibition of 5alphaR1 and 5alphaR2 activity was only observed with free fatty acids: esterified fatty acids, alcohols as well as sterols assayed were inactive. A specificity of the fatty acids in 5alphaR1 or 5alphaR2 inhibition has been found. Long unsaturated chains (oleic and linolenic) were active (IC(50)=4+/-2 and 13+/-3 microg/ml, respectively) on 5alphaR1 but to a much lesser extent (IC(50)>100 and 35+/-21 microg/ml, respectively) on 5alphaR2. Palmitic and stearic acids were inactive on the two isoforms. Lauric acid was active on 5alphaR1 (IC(50)=17+/-3 microg/ml) and 5alphaR2 (IC(50)=19+/-9 microg/ml). The inhibitory activity of myristic acid was evaluated on 5alphaR2 only and found active on this isoform (IC(50)=4+/-2 microg/ml).The dual inhibitory activity of LSESr on 5alpha-reductase type 1 and type 2 can be attributed to its high content in free fatty acids.
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Do saw palmetto extracts block human alpha1-adrenoceptor subtypes in vivo?:Prostate. 2001 Feb 15;46(3):226-32.Goepel M, Dinh L, Mitchell A, Schafers RF, Rubben H, Michel MC. Department of Urology, University of Essen, Essen, Germany.[PMID: 11170151]
BACKGROUND: To test whether saw palmetto extracts, which act as alpha1-adrenoceptor antagonists in vitro, also do so in vivo in man. METHODS: In a placebo-controlled, double-blind, four-way cross-over study 12 healthy young men were treated with three different saw palmetto extract preparations (320 mg o.d.) for 8 days each. On the last day, before and 2, 4 and 6 hr after drug intake blood pressure and heart rate were determined and blood samples obtained, which were used in an ex vivo radioreceptor assay with cloned human alpha1-adrenoceptor subtypes. RESULTS: Saw palmetto extract treatment did not result in alpha1-adrenoceptor subtype occupancy in the radioreceptor assay. Although the saw palmetto extracts caused minor reductions of supine blood pressure, they did not affect blood pressure during orthostatic stress testing and did not alter heart rate under either condition. Moreover, plasma catecholamines remained largely unaltered. CONCLUSIONS: Despite their alpha1-adrenoceptor antagonist effects in vitro, therapeutically used doses of saw palmetto extracts do not cause alpha1-adrenoceptor antagonism in man in vivo.
Effect of the lipidosterolic extract of Serenoa repens (Permixon) and its major components on basic fibroblast growth factor-induced proliferation of cultures of human prostate biopsies.:Eur Urol. 1998;33(3):340-7.Paubert-Braquet M, Cousse H, Raynaud JP, Mencia-Huerta JM, Braquet P. Bio-Inova Euro Lab Research Laboratories, Plaisir, France.[PMID: 9555564]
OBJECTIVE: To assess the effect of the lipidosterolic extract of Serenoa repens (LSESr) on in vitro cell proliferation in biopsies of human prostate MATERIAL AND METHODS: Cell proliferation was assessed by incorporation of [3H]thymidine followed by historadiography. RESULTS: Basic fibroblast growth factor (b-FGF) induced a considerable increase in human prostate cell proliferation (from +100 to +250%); the glandular epithelium was mainly affected, minimal labeling being recorded in the other regions of the prostate. Similar results were observed with epidermal growth factor (EGF), although the increase in cell proliferation was not recorded in some cases. Lovastatin, an inhibitor of hydroxymethylglutaryl coenzyme A, antagonized both the basal proliferation and the growth factor-stimulated proliferation of human prostate epithelium (EGF, mean inhibition approximately 80-95%; b-FGF, mean inhibition approximately 40-90%). Geraniol, a precursor of both farnesyl pyrophosphate and geranylgeranyl pyrophosphate, and farnesol, the precursor of farnesyl pyrophosphate, increased cell proliferation only in some prostate specimens, this effect being antagonized by lovastatin. LSESr did not affect basal prostate cell proliferation, with the exception of two prostate specimens in which a significant inhibition of basal proliferation was observed with the highest concentration of LSESr (30 micrograms/ ml). In contrast, LSESr inhibited b-FGF-induced proliferation of human prostate cell cultures; this effect was significant for the highest concentration of LSESr (30 micrograms/ml). In some prostate samples, a similar inhibition was also noted with lower concentrations. Unsaturated fatty acids (UFA), in the range 1-30 ng/ml), did not affect the basal prostate cell proliferation, only a slight increase in cell proliferation was noted in 1 prostate specimen. UFA (1, 10 or 30 micrograms/ml) markedly inhibited the b-FGF-induced cell proliferation down to the basal value. Lupenone, hexacosanol and the unsaponified fraction of LSESr markedly inhibited the b-FGF-induced cell proliferation, whereas a minimal effect on basal cell proliferation was noted. CONCLUSIONS: Despite the large variability in the response of the prostate samples to b-FGF, these results indicate that LSESr and its components affect the proliferative response of prostate cells to b-FGF more than their basal proliferation.
BPH Management with Saw Palmetto:
Saw Palmetto (Serenoa serrulata) is one of the most widely prescribed herbal medicines in Europe for the symptomatic relief of medically-diagnosed enlarged prostate. The prostate is a small circular gland positioned just below the bladder where urine is stored. The urethra passes through the middle of the prostate and provides a passage way for urine to pass through the penis.
Hormonal changes which occur during aging can cause the prostate to enlarge. Prostate enlargement is triggered by a form of testosterone called dihydrotestosterone (DHT). The enzyme 5-alpha reductase converts testosterone to DHT resulting in greater prostate enlargement.
50 to 60% of men aged between 40 and 60 may be affected by enlargement of the prostate due to alterations in hormone levels. The prostate gland is about the size of a walnut and is located at the base of the bladder. Through its centre passes the urethra, the tube that transports urine from the bladder out of the body. The prostate gland itself makes the seminal fluid that transports and nourishes sperm.
Benign prostatic enlargement is a male hormone (androgen) dependent disorder. As men age alterations in hormone levels can occur, leading to an increased concentration of dihydrotestosterone within the prostate.
Dihydrotestosterone is a very potent androgen derived from testosterone and is responsible for the over-production of prostate cells that result in prostatic enlargement. Testosterone and dihydrotestosterone are normally metabolised by enzymes to compounds that are then excreted. Elevated oestrogen levels inhibit the rate of excretion of these hormones from the prostate gland.
In addition, there appears to be elevated prolactin levels that lead to an increase in the uptake of testosterone by the prostate gland leading to an increased synthesis of dihydrotestosterone. Drugs that reduce prolactin levels reduce many of the symptoms of benign prostatic hypertrophy.
Most enlarged prostate's are benign - a condition known as benign prostatic hyperplasia (BPH) - and may be quickly and effectively managed with Saw Palmetto (Serenoa serrulata).
Numerous human trials report that saw palmetto improves symptoms of benign prostatic hypertrophy (BPH) such as nighttime urination, urinary flow, and overall quality of life, although it may not greatly reduce the size of the prostate. The effectiveness may be similar to the medication finasteride (Proscar®) with fewer side effects. Although the quality of these studies has been variable, overall they suggest effectiveness. Saw palmetto has not been thoroughly compared to other types of drugs used for BPH, such as doxazosin (Cardura®) or terazosin (Hytrin®). Most available studies have assessed the standardized saw palmetto product Permixon®. Although a 2003 study by Willetts et al. reports no difference between the effects of saw palmetto and placebo in 100 men over a 12-week period, overall the weight of available scientific evidence favors the effectiveness of saw palmetto.
Prostate enlargement puts pressure on the urethra by clamping it and causing the following symptoms,Symptoms of benign prostatic enlargement maybe the same symptoms as prostate cancer, which requires medical treatment. It is imperative that medical advice is sort for definite diagnosis:
Frequent and urgent urination, including night-time urination (nocturia:the need to get up and pass urine in the night)
Urinary frequency or urgency
Weak or interrupted urination stream,Weak stream of urine
Painful urination
Less force of urination,Small voided volumes of urine
Difficulty urinating (retaining urine in bladder,Feeling of incomplete bladder emptying)
Increased risk of urinary tract infection
Loss of urinary control,Stopping and starting of urine
Blood in urine
Urinary hesitancy on commencement of urination flow
Prolonged voiding time
Post-voiding urine dribble
A double-blind randomised controlled trial also reported beneficial effects of saw palmetto for androgenic alopecia (hair loss).
Serenoa (Serenoa serrulata, Hook F), commonly called Saw palmetto (or Sabal), is a dwarf palm native to the East Coast of North America. By the end of the 19th century the berries of this plant had gained a reputation for use in the treatment of urinary and reproductive dysfunction and as an aphrodisiac.
In the first half of this century the berries were cited in the USA Pharmocopoeia for the treatment of dysuria. The traditional therapeutic profile of the berries includes tonic, immune stimulant, expectorant and sedative properties. However, it is the anti-inflammatory and urinary antiseptic properties of the berries which have been emphasised in modern research studies, particular attention being paid to its use in treatment of BPH. A number of double-blind studies have been undertaken with Serenoa extracts for the treatment of patients with BPH. These show a significant improvement in signs of the condition compared with placebo within 90 days.
Attention has focused on beta-sitosterol as the principle active constituent of the berries, lipophyllic extracts of which have been shown to inhibit the activity of 5-alpha reductase. This is the enzyme in the prostate that is responsible for the conversion of testosterone to dehydrotestosterone (DHT), high concentrations of which promote prostate cell division.
Therapeutic Uses:
Saw Palmetto provides effective relief from the symptoms of BPH. BPH is characterised by an enlargement of the prostate gland that makes urination difficult and uncomfortable. As the prostate gland enlarges, it puts pressure on the urethra that carries urine from the bladder.
The most common symptoms of BPH include the need for frequent daytime and nocturnal urination, delayed onset of urination, dribbling after urination, and reduced urinary stream. BPH will affect over 50% of men in their lifetime with symptoms usually developing around the age of 50. The majority of men over 60 are considered to have urinary symptoms attributable to BPH and by the age of 80 there is an 80% chance of experiencing urination problems caused by BPH. There have been over 15 years of reported open and observational studies and more than 10 double blind placebo controlled clinical trials on extracts of Saw Palmetto for the treatment of BPH. There is no evidence to suggest that Saw Palmetto is effective in preventing BPH or reducing the risk of prostate cancer.
The normal prostate is about the size of a walnut. It lies just below the bladder at the base of the penis and is wrapped around the urethra, the tube that urine is excreted down. After the age of 40 the prostate naturally starts to enlarge in most men. This is known as BPH. BPH is most common from the age of 50. Symptoms of BPH include frequent urination, urgency to urinate, and need to pass urine at night (nocturia) , poor stream, incomplete emptying of the bladder and difficulty in stopping urination. Approximately 90% of men over 85 years of age have BPH.
Standardized extracts of Saw Palmetto have been shown in clinical studies to play a role in the treatment of the symptoms of BPH. A systematic review of Saw Palmetto including 18 randomised clinical studies, 16 of which were double-blind, involving a total of 2,939 men with BPH demonstrated that the herbal extract lead to a decrease in urinary symptoms and nocturia. There was also a reported increase in peak urine flow. A review of these studies was published as a Cochrane systematic review (Wilt T J et al. Serenoa repens for the treatment of Benign Prostatic Hyperplasia, In: The Cochrane Library, Issue 3, 2001).
The Saw Palmetto extract appears to control the hormonal changes that can lead to the growth of the prostate gland with age. Saw Palmetto helps to counteract the effects of oestrogen and progesterone on the gland. Its main action is to block the enzyme that converts the male hormone testosterone to a more active form, which stimulates the prostate gland to increase in size. This enzyme becomes more active with age.
Male Sexual Health and the Prostate Gland :
Men health is often neglected. It is a subject which men find difficult to discuss in a sober state unless tempered with toilet humour. It often falls to women to look after the health of the family as men seem to have a distinct dislike of visiting their doctor.
Now I could talk about how men have an increased risk of heart disease compared to women but that would be boring. I will discuss heart disease later in the year. Instead I＊m going straight to the crux, so to speak, of male health.
Men are different to women in several ways, but we will be focusing on the main physical differences. So prepare to wipe a tear from your eye, cross your legs, and read on＃
I am talking about the male sexual organs (penis, testes/testicles and prostate gland), and testosterone, the male hormone.
Male Health M.O.T.
Think of the male body as a car. Food is fuel. Is yours 2* or super unleaded? How we use our bodies affects their condition. Do you thrash yours, run it into the ground, go too fast? Food, alcohol, drugs, sleep, mood and exercise all affect whether your body is a sports car with tuned engine and alloy wheels. Or a clapped out fiesta complete with patches of rust and a flat tyre! When was the last time you had an MOT?
Most men don＊t like visiting their doctor or health professional. They hope that whatever problem they have will just＃go away＃ but when was the last time you ignored that squeak in your engine which turned into a breakdown? Forget to service your cam belt and before you know it the thing snaps under the strain and your engine becomes scrap metal.
Below is a basic MOT for your intimate parts to be undertaken by yourself or, if you are in the mood, a friend.
1. Check pubic area, penis and scrotum for any marks, moles, patches of unusual skin, redness, sores or scabs. Old moles require checking for changes in size and appearance. Found something suspicious or a changed mole? FAIL 每 seek a qualified second opinion.
2. Check penis itself. Is there any discharge? Unless the fluid is clear then that suggests a possible infection or sexually transmitted disease. FAIL 每 seek immediate attention from GP and no sex without a condom.
3. Check the testicles by feeling the size and shape of them. If one or both feels swollen or has a lump then you may have a problem. FAIL 每 seek a qualified second opinion.
If everything was clear and "normal" then that is a conditional PASS. Retest due monthly.
The Ring Do-nut Gland
Have you heard of the prostate gland? Do you know where it is and what it does?
The prostate is a ring doughnut-shaped gland which is just below the bladder. Through the hole in the middle passes a tube which leads from the bladder to the outside of your body at the tip of the penis. This tube is the passageway for urine and semen.
The prostate should not cause you any problems but in some men it becomes enlarged due to changes to the male hormone testosterone in middle age. 50% of 60 year olds are likely to have some symptoms. Enlargement is referred to as Benign Prostatic Hyperplasia (BPH). This means that the prostate has grown, making the hole passing through the middle smaller. When this happens passing water and even ejaculating can become difficult.
Do you have trouble starting to pass water? Is the flow slow or trickling? Do you dribble urine after finishing? Do you have to get up in the night to go to toilet?
If you can answer yes to any of these questions, and you are finding the symptoms irritating then you might like to seek further advice from a health practitioner, or your GP. Men with suspected prostate enlargement will be given a blood test and a physical examination to rule out more serious conditions. Remember that your doctor is there to help you. Ask for help and get treated quickly.
If the symptoms are mild, or in the early stages you might like to consider herbal medicine. The most common herb used is saw palmetto (Serenoa serrulata) which works by acting directly on the prostate to relieve some of the symptoms.
If your symptoms are more serious you may need an operation. This usually involves increasing the size of the hole which passes through the prostate.
Taming of the Shrew
If you have managed to read this far congratulations! If you have skipped down and started reading here then you may want to prepare yourself because now it is time for the ultimate test. The topic of conversation may be about to get even worse. It is time for the most taboo subjects of male health. I am talking about altered arousal. Young men may find that they are too excitable and older men may feel that they can not get excited enough!
Let＊s start with the idea that a man is too aroused. This can lead to premature ejaculation. You can thank the monks of the Middle Ages, and the Victorians for their strict views on purity, and therefore their research into herbs which reduce desire. One traditional herb used by monks to reduce impure thoughts was Vitex agnus castus. Also try adding sour foods to your diet such as citrus fruit and vinegar.
Now for the piece de resistance. It is a fact＃ All men occasionally have trouble maintaining an erection. Particularly after drinking alcohol, or taking other drugs/medications. If you＊ve had this problem occasionally or just the once it＊s not likely to be anything serious and you can relax safe in the knowledge that you are not the only one it is happened to.
However if you have found this to be an ongoing situation, or it＊s getting worse then there are many possible causes which can be ruled out by discussing them with your health practitioner. Firstly check the side-effects of any prescription drugs that you are taking. It might be as simple as that and your doctor may be able to suggest and alternative drug or treatment.
If drug side-effects have been ruled out then one common cause is mental or emotional stress. You may feel stressed or worried about money, work, or your home life. This will have an effect on your desire. The most effective remedy is talking, to relieve the feeling of being alone and unable to cope, and maybe even to find solutions to your problems. Discussing your needs and concerns with your partner may also help. Talking to a counsellor or sex therapist may well be beneficial. In conjunction herbs can act as very effective relaxants helping you to overcome short-term feelings of anxiety, fear, or sad mood. Try Matricaria recutita (German Chamomile), Turnera diffusa (Damiana), or Melissa officinalis (Lemon Balm) amongst others.
Desire can also be improved by taking some mild herbal aphrodisiacs such as Panax ginseng (Chinese Ginseng), Schisandra chinensis, or Serenoa serrulata,
Another cause of erection problems actually physical and due to poor circulation. As we get older our blood vessels get in bad condition and this can have an effect. Diabetics may suffer from damaged nerves (reducing feeling) and damaged blood vessels if their blood glucose is not controlled effectively.
Treatment includes improving your diet, getting some moderate exercise and by taking some herbs to strengthen your circulatory system. Try Ginkgo biloba. You might also like to include garlic, ginger and chilli in your food.
Herbal Therapy for BPH:Classical Literature and Combinations
Recent Research Update:
Benign prostatic hyperplasia (BPH) is a common problem of aging for men. It has been proposed that the disorder has two phases, one that involves no clinical signs and the other that is manifested as disorders of urination from urinary tract obstruction by an enlarged prostate. In the first phase, there are microscopic changes within the prostate that may occur as early as the fourth decade of life and these may then be followed by macroscopic changes, namely enlargement of the prostate that typically begins during the fifth or sixth decade of life. However, clinical signs of the disorder occur only if the enlargement is substantial and becomes complicated by other disorders, such as prostatitis, or if the gland becomes hardened or deformed. The progression to clinical disease is most often seen after age 60. It is further suggested that while nearly all men will experience the microscopic changes in the prostate if they live long enough, only about half will experience prostate enlargement, and, of those, only about half will develop clinical symptoms. The question then arises: what causes the relatively common occurrence of prostate changes that lead to clinical disease?
Epidemiological studies have demonstrated that many of the same risk factors associated with cardiovascular diseases apply as risk factors for BPH. These risk factors include obesity, hypertension, and diabetes. The diabetes connection is considered especially strong; the risk is non-insulin dependent diabetes mellitus (NIDDM), which often involves excessive insulin levels, a possible direct contributor to the growth of the prostate. As with cardiovascular disease, both exercise and moderate alcohol consumption appear to be protective for BPH. The influence of cigarette smoking on BPH has been unclear: some studies indicate a protective effect (there is a protective effect of smoking for ulcerative colitis that is well-established, so this result is not to be rejected out of hand), but other studies indicate a negative impact, at least for heavy smokers.
Hormones affect the development and progression of BPH. Men with liver cirrhosis have a lower incidence of BPH than those who have normal liver function, probably because the liver damage reduces the metabolism of hormones to compounds that adversely influence BPH. Not all hormonal influences on BPH have been determined, but both sex hormones (estrogen, testosterone, prolactin) and insulin have been shown to have an effect thus far. In particular, it is thought that the conversion of testosterone to 5-alpha-dihydrotestosterone (DHT) may be a significant risk factor for BPH. The drug Finasteride suppresses DHT production by inhibiting the enzyme (5-alpha reductase) that converts testosterone to DHT, and this drug has been shown effective in reducing symptoms of BPH. DHT, produced in sebaceous glands, is also a contributor to male-pattern balding.
It is not known whether herbal, nutritional, or drug treatments for cardiovascular disease would also have an impact on BPH. However, the alpha-adrenoceptor agonist drug (Doxazosin) used for treating hypertension also appears to have therapeutic value for BPH.
Oriental Treatment:
Chinese medical literature has been relatively silent on the problem of BPH. Disorders of urination have been noted since ancient times, classified as "lin" syndromes, which involve obstruction of urinary flow. In descriptions of the lin syndromes, most times the obstruction of urination is described as accompanied by symptoms that are not characteristic of BPH, such as blood in the urine or passing of stones or cloudy urine. Therefore, while BPH may have been experienced and treated as one of the lin syndromes, it is unclear whether any of the therapies were specific for BPH.
Chinese clinical researchers have addressed the problem of prostate disorders, but usually include a broad range of problems-dominated by acute prostatitis-in the study group, for which differential diagnosis is applied. Typical therapeutic categories are: qi and blood stasis (obstructed circulation), damp-heat accumulation (swelling and fluid accumulation), and kidney deficiency syndrome (problems of aging; weak function of the kidneys). The formulas administered vary considerably, but most formulations for treating qi and blood stasis include vacarria (wangbuliuxing); virtually all formulations for treating damp-heat and urinary obstruction include plantago seed (cheqianzi). Kidney deficiency formulations (subdivided into yin and yang deficiency categories) for prostate disorders usually incorporate herbs for treating blood stasis and damp-heat as secondary components.
It is possible that the microscopic changes in the prostate in the early development of the disease process are consistent with microcirculation changes that are normally treated with blood vitalizing herbs. Prostate enlargement is consistent with a damp-heat syndrome, since this syndrome is commonly associated with non-painful swelling in the lower abdomen. The final development of clinical symptoms of urination disorders corresponds closely with Chinese depictions of significant blood stasis and damp-heat coupled with weakening kidney qi. Thus, the three main diagnostic categories for prostate disorders described in the Chinese medical literature may have relevance to BPH in terms of its development over several decades, with a progression of each of the three syndromes. Based on such a scenario, the therapy for clinical BPH with Chinese herbs would involve a combination of treating kidney deficiency syndrome as a solution for the constitutional disorder associated with aging, along with blood vitalizing and damp-heat removing herbs as a treatment for the swollen prostate.
In accordance with traditional Chinese medicine doctrine, each patient should be treated on the basis of his actual syndrome rather than by a set formula. For example, yin deficiency fire (treated by modification of Zhi Bai Dihuang Wan) or spleen and lung qi deficiency (treated by modification of Buzhong Yiqi Tang) could each be factors contributing to urinary disorders such as those seen with BPH. Nonetheless, most cases of BPH in essentially healthy men are likely to correspond to the disorder categories generalized above. Although the Chinese herb formulas appear to have the potential to increase testosterone levels (see Appendix 2), this change may not be sufficient to adversely affect BPH, especially if the herbs can also suppress conversion of testosterone to DHT, as suggested for Western herbs used in treating BPH.
Western Herbal Remedy:
The treatment of BPH became a medical issue during the same time that cardiovascular disease therapy came to the fore, mainly during the 1970s. In Germany, where herbal therapy (phytotherapy) was still pursued by the pharmaceutical industry, the use of herbs was investigated at the same time that other researchers pursued surgical and drug options.
Dr. Hildebert Wagner, one of the leading proponents of phytotherapy (working at the Institute for Pharmaceutical Biology at the University of Munich), proposed investigation of the active components in Sabal serrulata for BPH in 1981. This herb, now referred to as Serenoa serrulata or, more commonly, as Serenoa repens, had been popular in the U.S. during the 19th century as a treatment for a variety of urino-genital disorders and had been mentioned as a treatment for prostate problems as early as 1899. The fruit of the plant, a small palm called saw palmetto (palmetto is Spanish for small palm; it has sharp, saw-like leaves) that is abundant in Florida, was used as a food for farm and ranch animals and as a medicine for humans. Research into the effects of Serenoa in Germany, and subsequently in many other European countries, appeared to confirm a positive action on BPH, so that this became the principal use of the herb. By 1995, saw palmetto had become one of the 10 most extensively-used Western herbs, with almost all of the commercial supplies going into products for BPH. The fruit is rich in sterols, which appear to be the primary active constituents. Although various proposals have been made as to how the sterols might affect BPH, the mechanism of action is still not clearly established. It is thought that the sterols may have, as one mechanism of action, the inhibition of DHT production.
At the same time, other Western herbs were investigated, with most attention falling to pumpkin seeds (Cucurbita pepo), nettle root (Urtica dioica or Urtica urens), bee pollen (particularly that from the rye plant), African potato (tubers of Hypoxis rooperi), and the large high-altitude African tree Pygeum africanum, also known as Prunus africanum. In most cases, but particularly with pumpkin seeds and African potato, the main active components are understood to be the sterols, such as beta-sitosterol, which has been used as a therapeutic agent for BPH by itself. Triterpenoids in pygeum have also been proposed to be active components, potentially having the action of reducing prostate swelling.
Among the Chinese herbs recommended for BPH, the iridoid glycosides may be the active components: these include aucubin from plantago seed, catalpol from rehmannia, and morroniside from cornus (an ingredient in the rehmannia formulas). Iridoids have not been found in the Western herbal therapies for BPH and represent a potential new area for future investigation. Iridoids are the recognized active constituents of the Western herb chaste tree berry, Vitex agnus costus, which has been shown to reduce prolactin levels in women; elevated prolactin may be a risk factor for prostate enlargement in men. Triterpenoids found in vaccaria and alisma (an ingredient in rehmannia formulas) could contribute to their therapeutic effects, in a manner similar to those suggested for pygeum.
Today, products for BPH remain one of the primary commercial successes in the field of herbal medicine. The herbs are sold either individually or in combination products with 2 or 3 of the ingredients. The two most commonly-used substances, both as single herbs or in combination products, are saw palmetto and pygeum. The National Institutes of Health (NIH) have taken note of this and proposed to fund a large study of saw palmetto and pygeum (see Appendix 3). The usual amount of saw palmetto provided in clinical studies is 320-480 mg of extract per day, in two divided doses. The usual amount of pygeum extract used in clinical trials is 100-200 mg/day. Treatment time is from 45 to 90 days to obtain significant improvement in symptoms; treatment time of 6 months has been reported to have a lasting effect for at least 18 months. Adverse effects of the herb therapies for BPH have not been reported.
Combinations for treatment Index:
Appendix 1. Rehmannia Eight Formula and Its contents:
Rehmannia Eight Formula is presented with some variations among the Chinese texts. The following is a representative formulation that can be used as a starting point for discussion of the ingredients and their effects:
Rehmannia(shudi) 24%,Cornus(wuzhuyu) 16%,Dioscorea(shanyao) 16%,Alisma(zexie) 12%,Hoelen(fuling) 12%,Moutan(mudanpi) 12%,Aconite(fuzi) 4%,Cinnamon(guizhi) 4%
The lead ingredient is cooked rehmannia, which is described in the Chinese tradition as a nutritive agent, alleviating dryness and promoting the functions of the liver and kidney systems (see Appendix 2 for further details). The remaining herbs of the formula can be understood as supporting the function of rehmannia. The small amounts of processed aconite and either cinnamon bark (rougui) or cinnamon twig (guizhi) serve as the hallmark of this particular rehmannia formula, one of numerous rehmannia-based combinations relied upon by Chinese doctors.
The characteristics of rehmannia, for which the processed form (shudi) is used here, are: rich and moist quality, sweet taste, and warming nature. Rehmannia would be too thick and rich to offer as a single herb: it is said to have a "cloying" quality (being very sweet and moist). Therefore, the herb is combined with others that can balance and harmonize its actions.
In particular, three of the herbs in this formula help to balance the rich, moist quality of rehmannia: alisma, hoelen, and dioscorea. These herbs:
promote the function of the digestive system (thus helping it handle the rich tonic, which is otherwise somewhat difficult to digest, like a rich dessert);
get rid of any excess moisture that may already be present (which, when combined with the moist rehmannia, would make an uncomfortable condition of fullness and tiredness); and
assist the functions of the kidney system in a manner that compliments the tonic effect of rehmannia, namely by promoting its draining action (aiding elimination via urination).
Chinese doctors point to the role of alisma in dissolving greasiness, which is useful in countering the thick, moist quality of rehmannia; additionally, it removes (via urination) turbid materials that accumulate in the body. Dioscorea also helps the body to eliminate excess moisture, especially from the digestive tract (where diarrhea can occur if the moisture accumulates). Hoelen is depicted as absorbing moisture, like a sponge, from places of accumulation, to deposit it where it is needed (e.g., to areas that are dry or areas that will lead to its elimination).
The book Commonly Used Chinese Herb Formulas with Illustrations gives a listing of the Kanpo applications for Rehmannia Eight Formula as follows:
1.Nephritis (nephrosclerosis, nephrolithiasis, nephrotuberculosis), pyelitis (nephroatrophy), albuminuria, and edema.
2.Cystitis, cystolithiasis, cystotuberculosis, senile cystoatrophy, prostatomegaly, dysuria, urinary incontinence, and nocturia.
3.Diabetes and urinary incontinence.
4.Cerebral hemorrhage, arteriosclerosis, hypertension, and hypotension.
5.Neurasthenia, amnesia, nocturnal emission, uncontrolled emission, impotence, and inappropriate erection of the penis.
6.Lumbago, sciatica, deformed vertebra, numbness of the legs, and beriberi.
7.Cataract, glaucoma, decrease of eyesight, and keratitis.
8.Eczema, tinea, senile itching, vaginal itching, dry skin, and urticaria.
9.Chronic gonorrhea, rectoptosis, climacteric disturbance and related disorders.
The first three groups of indications are related to urinary system disorders (diabetes is included as a cause of frequent urination). In the original text presentations (Shanghan Lun and Jingui Yaolue), the principal applications of the formula were for syndromes that included urination disorders. The underlying causes of these urinary disorders were described in terms understood many centuries ago; today, it is believed that various diseases of the kidney, bladder, and prostate are responsible for most of the changes in urination.
For the most part, the other indications given for the formula (items 4-9) are more recent applications (developed during the past 50 years). Some of these indications can be predicted on the basis of the herb ingredients and Chinese medical theories. For example, the kidney system is said to control sexual function and influence the lower back and legs (e.g., symptoms of impotence, low back pain, sciatica, and knee swelling would often be interpreted as arising from dysfunction of the kidney system), thus helping to explain most of the items listed in 5 and 6. Disorders that typically arise as part of the aging process, such as the cardiovascular diseases (item 4), the eye disorders (item 7), and the dry skin problems (item 8), are addressed, according to Chinese doctrine, by nourishing the kidney and liver, as accomplished by the rehmannia-based formulas.
In the book, Kampo Treatment for Climacteric Disorders (22), Rehmannia Eight Formula is described as one for "conditions marked by degenerative changes and decline in functions, commonly associated with aging...." As a major indication, "limpness or pain in the lumbar region or knees" is cited, along with sensitivity to cold, abnormal urination, and a variety of symptoms such as impairment of vision or hearing, decline in mental abilities, dry itchy skin, and shortness of breath. The authors claim that the formula "can be more effective than conventional drug therapy in controlling and preventing complications of diabetes, such as peripheral neuropathy, nephropathy, and retinopathy." While the focus of their book is on climacteric syndrome (menopause), they also mention the "male menopause" conditions of impotence, prostatitis, and prostate hypertrophy as additional applications of the formula.
In the book 100 Famous and Effective Prescriptions of Ancient and Modern Times (23), which depicts the practices in mainland China, Rehmannia Eight Formula is said to have the following indications:
Insufficiency of kidney yang marked by lumbago, lassitude of the feet, cold feelings in the lower part of the body, cramping sensation in the lower abdomen, difficulty in urination or plenty of urination, impotence, pale and thick tongue proper, weak and fine pulse, as well as cough due to phlegm retention, diabetes, edema, chronic diarrhea...etc.
For modern indications, the book relates a list somewhat similar in nature, though shorter, than that given by Kanpo practitioners: chronic nephritis, hypertension, diabetes, prostatic hyperplasia, postpartum retention of urine, pulmonary emphysema, neurosis, menopausal syndrome, and senile cataract. The book goes on to mention two clinical trials of the formula, one for treatment of cataract and the other for dysuria (due to prostatic hyperplasia); both are claimed to show positive results.
Appendix 2. Rehmannia Phytochemicals:
The main active constituents of rehmannia are iridoid glycosides. These are monoterpenes that have a glucose molecule attached. Catalpol was the first of these isolated from rehmannia (in 1969), and is the one present in largest amounts. There are more than a dozen iridoids that have been isolated from rehmannia, but the others are present in relatively minor quantities. In a study of several samples of rehmannia, it was found that catalpol makes up about 3-11% of the undried root content (depending on the growing conditions), with considerably less (about 1-2%) in the dried root: the drying process evidently destroys this component, converting it into another compound that may or may not be active.
The pharmacological action of catalpol and the other iridoids is not fully established, but it appears that their main function is to stimulate production of adrenal cortical hormones. These hormones have anti-inflammatory action (explaining the claimed benefits of rehmannia for asthma, skin diseases, and arthritis) and are involved in the production of sex hormones (explaining the claimed benefit of treating menopause, impotence, and other signs of hormone deficiency). It is possible that anti-inflammatory effects could explain its early use in mending injuries, and the androgens that the adrenal gland might yield could increase muscle mass. The adrenal steroids may then serve as precursors to production of sex hormones. Rehmannia Eight Formula was tested in aged rats. It was shown to increase estradiol level of the serum in female rats and to raise serum testosterone in male rats.
One of the iridoid glycosides that is found in small amounts in rehmannia and scrophularia is aucubin. It is very similar to catalpol and is also an active ingredient of the rarely used herb Acuba japonica, a close relative of cornus (which contains secoiridoid glycosides) that is used in many rehmannia formulas; aucubin is also present in the more commonly used plantago seed. Both aucubin and geniposide have been shown to have liver-protective actions.
Appendix 3. Alternative Therapies for Benign Prostate Symptoms-Clinical Trials Consortium:
The Division of Kidney, Urologic and Hematologic Diseases (DKUHD) of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Center for Complementary and Alternative Medicine (NCCAM), and the Office of Dietary Supplements (ODS) invite cooperative agreement grant applications to establish a research consortium to conduct a randomized controlled clinical trial of Serenoa repens (saw palmetto) and Pygeum africanum in men with benign prostatic hyperplasia (BPH). The plan is to spend $29 million over the next seven years.
As the population ages the number of men with lower urinary tract symptoms indicative of BPH is expected to increase substantially. The segment of the United States population that utilizes alternative and complementary approaches to disease prevention and management is also increasing rapidly, including the use of phytotherapy to control the symptoms of BPH. The most common phytotherapeutic agent is Serenoa repens or saw palmetto. Pygeum africanum is also frequently used in this country for the same purpose. Little is known, however, about the long-term effects of these agents on the lower urinary tract symptoms experienced by men with BPH since rigorously conducted clinical trials for these agents have not been conducted.
In order to determine the effect of Serenoa repens and Pygeum africanum on the clinical progression of BPH the NIDDK and the NCCAM plan to establish a clinical trial consortium to conduct a large simple placebo-controlled clinical trial of these two agents comparing saw palmetto to placebo, and Pygeum to placebo. A secondary analysis will include head-to-head comparison of the two phytotherapy agents. The collaborative research group will consist of Clinical Evaluation and Treatment Centers (CETCs) to design and conduct the clinical trial and a single Data Coordinating Center (DCC) to collect, store, and analyze data generated by the CETCs.
More than one-half of the men 50 years of age or older have lower urinary tract symptoms associated with the development of benign prostatic hyperplasia (BPH). The condition accounts for at least 1.7 million office visits per year in the United States with estimated health care costs exceeding $4 billion a year. In addition, these symptoms have been shown to have a significant negative impact on patient-reported quality of life and psychological well-being. The use of alternative therapeutic agents to relieve the symptoms of BPH is increasing very rapidly. In 1996 extracts of the saw palmetto berry was the 9th most common herbal remedy sold in the U.S increasing to the 5th most common in 1997. It is anticipated that the use of alternative therapies for BPH will continue to increase substantially as the U.S. male population continues to age.
Despite the widespread use of phytotherapy for BPH in the United States, most physicians are reluctant to either discuss or recommend their use since only a modest number of published reports have appeared in the peer-reviewed medical literature about their efficacy. Moreover, very few have met rigorous standards for reporting the results of clinical trials. Nonetheless, the available literature supports the hypothesis that these compounds may have some beneficial effects on BPH symptoms. This is supported by a recent meta-analysis that suggests that Saw palmetto improves urinary flow-rate and nocturia in men with symptoms of BPH. However, there are no statistically significant reports of rigorously conducted clinical trials on the long-term effects (both beneficial and adverse) and on patient-reported outcomes.
The objective is to determine if Serenoa repens and Pygeum africanum prevent the clinical progression of BPH, as defined by the development of one of the following: acute urinary retention, renal insufficiency (due to BPH), recurrent urinary tract infections, incontinence, or an increase in the American Urological Association (AUA) symptom score index of four or more points. This definition of the clinical progression of BPH is identical to that used in a soon-to-be-completed clinical trial supported by the NIDDK, the Medical Therapy of Prostatic Symptoms (MTOPS) Trial. Results from the MTOPS Trial, in particular the event rate among the placebo group, will be made available to investigators participating in this consortium to assist in refinement of the trial design. The investigators participating in this consortium will design and conduct a large simple clinical trial. It is envisioned that the clinical trial will require a total of approximately 3,100 men with BPH who will be randomized over a two-year period. The clinical trial will be double-masked and placebo controlled. It is expected that each CETC will recruit and follow-up 300 men for the duration of the trial. Men will be followed for a minimum of four (4) years and a maximum of six (6) years post-randomization. Innovative methods will be required to implement this clinical trial including recruitment of a large number of men with symptoms of BPH, use of multiple strategies to promote long-term adherence to these agents, maintenance of high rates for clinic visits, and complete ascertainment of endpoints
Saw palmetto extract (SPE) should now be considered a treatment option for men with symptomatic BPH, absent complications of the disorder. SPE is extremely safe; it is likely to exert positive effects; many patients want it; and more potent remedies, i.e., drugs or surgery, are generally not required in most BPH cases. A recent meta-analysis of SPE trials from Europe (where nearly all previous studies originated) was published in a recent issue of the Journal of the American Medical Association concluding that SPE improves urinary flow and decreases prostate symptoms in men with BPH.
Non-malignant hypertrophy of the prostate affects slightly more than half of all men between the ages of 40 and 60. For these men, urination is more difficult; they experience incomplete emptying of the bladder during urination, and painful and more frequent urination at night. Infection, incontinence and urinary bleeding usually follow. Scientists associate this disease with an excess of testosterone in the form of dihydrotestosterone (DHT). Testosterone is transformed in to DHT by 5-alpha-reductase (5-AR), which increases in men as they grow older. Though extremely common, this disease can be prevented or treated if caught in time.
Willow-herb (Epilobium parviflorum), one of the fetish plants of the celebrated Maria Treben, has provided the traditional treatment for prostate problems. This plant is also an ingredient in the famous elixir, Swedish bitters. Recent research, notably at the Universit谷 de Lausanne, maintains that willow-herb has anti-inflammatory properties and an inhibitory effect on the enzymes that transform testosterone into DHT. It is therefore a tonic for the prostate.
Epilobium parviflorum is a plant used in Central Europe for the treatment of prostate disorders. Research has shown it to inhibit the conversion of testosterone to dihydrotestosterone (DHT) by activity of 5-alpha-reductase and aromatase((the group of enzymes that catalyze the conversion of testosterone to estradiol) ), two enzymes which are involved in the development of benign prostatic hyperplasia (BPH). The main polyphenols responsible for the inhibition of the these enzymes have been identified as oenothein A and oenothein B, which have been identified in Epilobium parviflorum plant extracts. Epilobium fatty acids contents also inhibits the production and release of prostaglandin D2 and of prostaglandin E2.
Actions: antiadenomic, anti-androgenic, anticancer, antiedemic, antiestrogenic, anti-inflammatory, antiprostadenomic (inhibitts prostate cancer), antiprostatitic, antitumor, bactericide, inhibits formation of dihydrotestosterone (DHT), liver protectant, prostate cancer preventative, reproductive alterative, uterosedative
Traditional use: benign prostatic hypertrophy (BPH), epididymitis, gynecomastia, nocturia, orchialgia, orchitis, painful menstruation, prostatitis, impotence, sex hormone disorders, testicular atrophy, urinary tract infection
Pygeum Africanum:
While saw palmetto extract is the far better known herbal medication to reduce the size of an enlarged prostate, pygeum may in many cases be superior for the treatment of the condition. Pygeum is an evergreen tree found in the higher elevations of central and southern Africa. Its bark, once used as a tea for relief of urinary disorders, has been found to contain not one, but three types of compounds that relieve the symptoms of prostate enlargement BHP (benign prostatic hyperplasia).
Pygeum contains three groups of active components: Phytosterols such as beta-sitosterol; pentacyclic triterpenoids, such as ursolic and oleanic acids; and ferulic esters of fatty alcohols, particularly the ferulic esters of docosanol and tetra-cosanol. The phytosterols constituents, beta-sitosterol and beta-sitosterone , particularly beta-sitosterol are found in numerous plants and are anti-inflammatory, inhibiting the synthesis of prostaglandins. Beta-sitosterol, the most important of the three, interferes with the formation of prostaglandins that cause inflammation and swelling in the prostate. Beta-sitosterol has been shown to be useful in cases of BPH by helping to reduce the normally elevated levels of prostaglandins in these patients. The elimination of the excess blood and vasal congestion helps reduce the size of prostate adenomas. The pentacyclic triter-penoids (urosolic, oleanic and crataegolic acids), also help inhibit inflammation by blocking enzymatic activity. They are effective anti-edema agents and also help increase the integrity of small veins and capillaries. The third active group, the ferulic esters (n-docosanol and tetracosanol), long-chain fatty acids, act by inhibiting the absorption and metabolism of cholesterol and combat enlargement by reducing levels of prolactin, a hormone which promotes uptake of growth-promoting testosterone in the prostate. Both prolactin and cholesterol increases binding sites for DHT in the prostate. BPH and other cases of enlarged prostates are characterized by containing abnormally high levels of cholesterol. Pygeum also inhibits protein kinase C-induced proliferation of prostate cells
European scientists were so impressed with reports of pygeum's actions that they began laboratory investigations into the active constituents in the bark. This led to the development of the modern lipophilic (fat soluble) extract used today.
Pygeum africanum extract is available in many countries, including those in central and eastern Europe, for the treatment of mild to moderate BPH. Its efficacy and acceptability have been demonstrated in numerous open and placebo-controlled studies in large populations. The present open three-centre efficacy and safety study was conducted according to common protocol at urology clinics in the Czech and Slovak Republics and in Poland, in order to confirm the therapeutic profile of Pygeum africanum in conditions of daily practice, using International Prostate Symptom Score (IPSS) and flowmetry assessments. The changes in subjective scores, IPSS and QoL (quality of life) after the two-month treatment period were highly statistically significant with mean improvements of 40% and 31%, respectively. Nocturnal frequency was reduced by 32% and the mean reduction was again highly statistically significant. Mean maximum urinary flow, average urinary flow and urine volume were also statistically significantly improved, but the modest improvement in post-voiding volume did not reach statistical significance. The improvements, which exceeded those observed with placebo in earlier studies, were maintained after one month without treatment indicating an interesting persistence of clinically useful activity. Prostatic volume and quality of sexual life remained unchanged throughout. No treatment-related adverse effects were observed. In conclusion, under conditions of daily practice, Pygeum africanum extract induces significant improvement in IPSS and uroflowmetry parameters. These positive effects are accompanied by a very satisfactory safety profile with the overall result of a substantial improvement in QoL.
A study by Swiss researchers R. Hartmann et al. demonstrate that extracts of pygeum (Pygeum africanum Kalkman, Rosaceae) and nettle root (Urtica dioica L., Urticaceae) partially blocked the action of two enzymes involved in the body's production of dihydrotestosterone and estrogen. The in vitro (laboratory) study showed that both pygeum and nettle root extracts were effective in inhibiting these two enzymes (5alpha-reductase and aromatase) and that a combination of the two plant extracts was significantly more effective than either extract individually in blocking aromatase activity.
Stinging nettle (Urtica dioic) and the bark of Pygeum Africanum both have anti- inflammatory and decongestant (anti-edema) properties.
Nettle root extract was effective only at high concentrations, while pygeum extract showed "a much higher efficacy" at lower doses. The combination of the two extracts was as effective as pygeum against 5 a-reductase and significantly more effective than either against aromatase. This study supports the use of combinations of these two ingredients in the treatment of BPH. This is especially important because pygeum bark is both expensive and limited in supply, while nettle roots are easily produced on a large scale.
Stinging nettle root contains both acid and neutral polysaccharides (2 glucans, 2 glucogalacturonans, and 1 arabinogalactan); sterols (0.2-1% 3-b-sitosterol, 0.05每0.2% sitosterol-3-b-D-glucoside); 0.1每0.2% lectin U. dioica agglutinin or UDA composed of six isolectins; coumarin (approximately 0.002每0.01% scopoletin); phenolic acids, phenylpropanoid aldehydes, and alcohols; lignans (neo-olivil and derivatives); fatty acids; tannins; and monoterpenes and triterpenes (Bruneton, 1995; ESCOP, 1997; Leung and Foster, 1996; List and H"rhammer, 1979; Newall et al., 1996; Wichtl and Bisset, 1994).
Stinging nettle root reported increased urinary volume, increased maximum urinary flow, and reduced residual urine activities. Note: This preparation relieves the symptoms of an enlarged prostate without reducing the enlargement. Please consult a physician at regular intervals.
The British Herbal Pharmacopoeia reported prostatic action (BHP, 1996). Preliminary clinical observations of men after long-term treatment with an alcoholic extract of nettle root reported improvement of bladder outlet obstruction symptoms and decrease in post-voiding residual urine (Bruneton, 1995). A study of BPH patients treated with a nettle root alcoholic fluidextract reported a 66% decrease in residual urine; another study reported a reduction of nocturnal micturition frequency in patients over 60 years of age after six months of treatment with a nettle root alcoholic tincture at 5 ml daily (ESCOP, 1997; Leung and Foster, 1996). The active substances responsible for these actions are unknown, which makes quality control and chemical or biological standardization of extracts difficult (Bruneton, 1995; Wichtl and Bisset, 1994).
Uses:Stinging nettle root approved the internal use for difficulty in urination in benign prostatic hyperplasia stages 1 and 2.
ESCOP indicates its use for symptomatic treatment of micturition disorders [nocturia (excessive nighttime urination), pollakisuria (frequent urination), dysuria (painful urination), or urine retention] in BPH stages 1 and 2 (ESCOP, 1997). The French Herbal Remedies Notice to Applicants for Marketing Authorization allows two uses of nettle root: as an adjunctive treatment for the bladder outlet obstruction symptoms of prostatic origin, and to enhance the renal elimination of water (Bruneton, 1995). It is used as a diuretic for conditions of dropsy and also for early stages of prostatitis. In African medicine it is used to treat diarrhea and as an anthelmintic to expel intestinal worms (List and H"rhammer, 1979).
Corn Silk:
As a soothing diuretic, Corn Silk is helpful in any irritation of the urinary system. It is used for renal problems in children and as a urinary demulcent combined with other herbs in the treatment of cystitis, urethritis, prostatitis and the like. Ellingwood suggests Corn Silk in the following conditions: catarrhalcystitis, lithaemia(stones), bladder irritation, gonorrhoea, all catarrhal conditions of the urinary passages, dropsies due to heart disease, edema.
Constituents : Saponins, Allantoin, Sterols, especially [[beta]]-sitosterol and stigmasterol, the alkaloid hordenine, Vitamins C & K, cryptoxanthin, anthocyanins, plant acids.
Buchu (Barosma betulina):
The standard Buchus of commerce are obtained from three species: Barosma betulina, known as 'shorts'; B. crenulata, known 'ovals' and 'shortbroads,' and B. serratifolia, known as 'longs.' The leaves of the firstnamed are most valued and constitute the foliea buchu of the British Pharmacopoeia. The Hottentots use several species, all under the common name of 'Bucku.' The leaves have a rue-like smell, and are used by the natives to perfume their bodies. Buchu leaves are collected while the plant is flowering and fruiting, and are then dried and exported from Cape Town. The bulk of the Buchu exported to London from South Africa eventually finds its way to America, where it is used in certain proprietary medicines.
The principal constituents of Buchu leaves are volatile oil and mucilage (volatile oil: diosphenol (=buchu camphor), pulegone, (+) and (-) isopulegone, 8-mercapto-p-menthan-3-one, responsible for the black currant type odour; 8-acetylthiomenthone, piperitone epoxide (+)-menthone, (-)-isomenthone, p-cymol, limonene, terpineol, flavonoids: rutin, diosmin, hesperidin, quercitin and derivatives miscellaneous: vitamins of the B group) tannin and mucilage., also diosphenol, which has antiseptic properties, and is considered by some to be the most important constituent of Buchu its absence from the variety known as 'Long Buchu' has led to the exclusion of the latter leaves from the British Pharmacopoeia.
The Cape Government exercises strict control over the gathering of Buchu leaves and has lately made the terms and conditions more onerous, in order to prevent the wholesale destruction of the wild plants, no person being permitted to pick or buy Buchu without a licence. Cultivation experiments with Buchu have been made from time to time by private persons, and during the war experiments were conducted at the National Botanic Gardens, Kirstenbosch (near Cape Town), the result of which (given in the South African Journal of Industries, 1919, 2, 748) indicate that, under suitable conditions, the commercial cultivation of Buchu should prove a success, B. betulina, the most valuable kind, being the species alone to be grown. The plant is particularly adapted to dry conditions, and may be cultivated on sunny hillsides where other crops will not succeed.
Buchu has long been known at the Cape as a stimulant tonic and remedy for stomachic troubles, where it is infused in Brandy and known as Buchu Brandy. Its use was learnt from the Hottentots. It was introdueed into official medicine in Great Britain in 1821 as a remedy for cystitis urethritis, nephritis and catarrh of the bladder.
Buchu may be used in any infection of the genito-urinary system, such as cystitis, urethritis and prostatitis. Its healing and soothing properties indicate its use together with other relevant remedies in many conditions of this system, especially useful where dysuria is part of the symptom picture. The oil content may be too irritating for people with a history of major kidney disease. Ellingwood says that " it acts directly upon the urinary apparatus, stimulating the kidneys . . . by its tonic and restorative influence. It relieves irritation of the bladder and urethra, and is valuable in catarrh of the bladder, pyelitis and gonorrhoea."
Jupiter (Juniperus communis) and Indian corn stigma (zea mays) are excellent diuretics and help prevent inflammation of the gallbladder.
Juniper Berries make an excellent antiseptic in conditions such as cystitis. The essential oil present is quite stimulating to the kidney nephrons and so this herb should be avoided in kidney disease. The bitter action aids digestion and eases flatulent colic. It is used in rheumatism and arthritis. Externally, is eases pain in the joints or muscles.
Constituents :
Volatile oil, containing mainly myrcene, sabinene andx-pinene, with 4-cineole, p-cymene, camphene, limonene, [[beta]]-pinene, terpin-4--ol, y-terpinene, x-thujene.
Condensed tannins; (+)-afzelechin, (-)-epiafzelechin, (+)-catechin, (-)-epicatechin, (+)-gallocatechin and (+)-epigallocatechin l, 4-dimethyl-3-cyclohexen-l-yl, methyl ketone
Diterpene acids; myreocommunic, communic, sandaracopimaric, isopimaric, torulosic acids and other diterpenes such as geijerone. Miscellaneous; sugars, resin, vitamin C.
But without question, the ingredient that makes the leading contribution to our formula for prostate protection is extract of palmetto leaf or saw palmetto (Serenoa repens). In recent years, it has been extraordinarily popular in Europe and North America in the treatment and prevention of prostate problems. Researchers have discovered that this plant blocks 5-AR activity, thereby lowering production of DHT, which causes hypertrophy of the prostate. European studies have shown that in the treatment of non-malignant hypertrophy of the prostate, palmetto leaves are just as efficient as conventional synthetic drugs, though they do not have any undesirable secondary effects.
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fatty acid is released from monoacylglycerols through the action of monoacylglycerol lipase
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fatty acid is an organic acid having a chain of carbon atoms coupled to hydrogen atoms at the side and a hydroxyl radicle at one end
fatty acid is removed from the fatty acid synthetase complex by specific enzyme that catalyzes the hydrolysis of the fatty acyl
fatty acid is completely cleaved to acetyl
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Scientific References:
1.Research Update of Saw Palmetto.
2.Serenoa repens,Sabal serrulata,Saw Palmetto Herb Extract Benefit.
Claims & Warning:
Claims: Information this web site presented is meant for Nutritional Benefit and as an educational starting point only, for use in maintenance and promotion good health in cooperation with a common knowledge base reference...Furthermore,it based solely on the traditional and historic use or legend of a given herb from the garden of Adonis. Although every effort has been made to ensure its accurate, please note that some info may be outdated by more recent scientific developments......
Pharmakon Warning: The order of knowledge is not the transparent order of forms and ideas,as one might be tempted retrospectively to interpret it; it is the antidote....(Dissemination,Plato's Pharmacy,II.The Ingredients:Phantasms,Festivals,and Paints;138cf. Jacques Derrida.).
And as it happens,the technique of imitation,along with the production of the simulacrum,has always been in Plato's eyes manifestly magical,thaumaturgical:......and the same things appear bent and straight to those who view them in water and out,or concave and convex,owing to similar errors of vision about colors, and there is obviously every confusion of this sort in our souls.And so scene painting (skiagraphia) in its exploitation of this weakness of four nature falls nothing short of witchcraft (thaumatopoia), and so do jugglery and many other such contrivances.(Republic X,602c-d;cf.also 607c).
seminal trace...Saw Palmetto extract.Sabal serrulata extract.CAS.NO:84604-15-9.Mixed fatty acids.25%45%.M.F.C10H10O4.CAS.NO:67254-79-9.Total Fatty Acids. saw palmetto berry extract.Extract of saw palmetto,ext...
Phytochemical info of Saw Palmetto and Saw Palmetto Extract:
Introduction:
Temperature:
Scientific References:
Claims & Warning:
